Final Flashcards
1
Q
The endocrine system:
The endocrine and nervous systems are the major controllers
of the flow of information between different cells and tissues.
Endocrine and neurotransmitter cells synthesize hormones and
release them by specialized secretory pathways.
The hormones act on the producer cell (autocrine) or on neighboring
target cells including neurotransmitter cells, without entering the circulation
(juxtacrine and paracrine).
They may go to the target cell through the circulation (hormonal).
Neurotransmitter cells release neurotransmitters from nerve terminals.
The same neurotransmitters can be released to act as hormones
through the synaptic junctions or directly by the cell.
A
The endocrine system:
The endocrine and nervous systems are the major controllers
of the flow of information between different cells and tissues.
Endocrine and neurotransmitter cells synthesize hormones and
release them by specialized secretory pathways.
The hormones act on the producer cell (autocrine) or on neighboring
target cells including neurotransmitter cells, without entering the circulation
(juxtacrine and paracrine).
They may go to the target cell through the circulation (hormonal).
Neurotransmitter cells release neurotransmitters from nerve terminals.
The same neurotransmitters can be released to act as hormones
through the synaptic junctions or directly by the cell.
2
Q
Chemical classification of hormones
Hormone synthesis:
Protein hormone production often does not require special machinery.
Growth hormone, prolactin, and PTH are produced similarly to other secreted proteins.
Some Peptide hormones (insulin, ACTH, and glucagons) are produced by cleavage of a larger protein.
Other hormones with specific structures are generated by specialized enzymes.
Thyroid hormone is produced by iodination and coupling of tyrosine residues
of thymoglobulin,
Steroid hormones are produced from cholesterol.
A
Chemical classification of hormones
Hormone synthesis:
Protein hormone production often does not require special machinery.
Growth hormone, prolactin, and PTH are produced similarly to other secreted proteins.
Some Peptide hormones (insulin, ACTH, and glucagons) are produced by cleavage of a larger protein.
Other hormones with specific structures are generated by specialized enzymes.
Thyroid hormone is produced by iodination and coupling of tyrosine residues
of thymoglobulin,
Steroid hormones are produced from cholesterol.
3
Q
Mechanisms of hormone secretion:
Hormones: are released by endocrine glands and transported through the
bloodstream to tissues where they bind to specific receptor molecules and
regulate target tissue function.
Endocrine: It is internal secretion of hormones into the circulation to convey
information to target cells.
Exocrine: It is secretion outside the circulation, e.g., sweat glands or ducts that lead into the gastrointestinal tract.
Paracrine: When hormones act on neighboring hormone-producing cells or non- hormone-producing cells, e.g.: actions of sex steroids in the ovary.
Autocrine: When hormone acts on receptors located on the same cell.
Autocrine actions may be important in promoting unregulated growth of cancer cells.
Intracrine: Hormones can also act inside the cell without being released, an
intracrine effect.
Example: insulin can inhibit its own release from pancreatic islet B cells
and somatostatin can inhibit its own release from pancreatic D cells.
A
Mechanisms of hormone secretion:
Hormones: are released by endocrine glands and transported through the
bloodstream to tissues where they bind to specific receptor molecules and
regulate target tissue function.
Endocrine: It is internal secretion of hormones into the circulation to convey
information to target cells.
Exocrine: It is secretion outside the circulation, e.g., sweat glands or ducts that lead into the gastrointestinal tract.
Paracrine: When hormones act on neighboring hormone-producing cells or non- hormone-producing cells, e.g.: actions of sex steroids in the ovary.
Autocrine: When hormone acts on receptors located on the same cell.
Autocrine actions may be important in promoting unregulated growth of cancer cells.
Intracrine: Hormones can also act inside the cell without being released, an
intracrine effect.
Example: insulin can inhibit its own release from pancreatic islet B cells
and somatostatin can inhibit its own release from pancreatic D cells.
4
Q
Hormone interactions
Synergistic effects
When two or more hormones work together to produce a particular result, their effects are said to be synergistic.
Example: epinephrine and norepinephrine on the heart, each hormones separately produces an increase in cardiac rate.
Permissive effects
A hormone have a permissive effect on the action of a second hormone when it enhances the responsiveness of a target organ to the second hormone or when it increases the activity of the second hormone.
Example: Cortisol and catecholamines
Antagonistic effects
In some situations, the actions of one hormone antagonize the effects of another.
Example: insulin and glucagon.
A
Hormone interactions
Synergistic effects
When two or more hormones work together to produce a particular result, their effects are said to be synergistic.
Example: epinephrine and norepinephrine on the heart, each hormones separately produces an increase in cardiac rate.
Permissive effects
A hormone have a permissive effect on the action of a second hormone when it enhances the responsiveness of a target organ to the second hormone or when it increases the activity of the second hormone.
Example: Cortisol and catecholamines
Antagonistic effects
In some situations, the actions of one hormone antagonize the effects of another.
Example: insulin and glucagon.
5
Q
Mechanism of action of hormones:
Hormones released by endocrine glands and transported through the
bloodstream to tissues by binding to specific receptor and regulate target
tissue function.
Some hormones bind cell surface receptors,
e.g., insulin, growth hormone, prolactin.
Some hormones bind to intracellular receptors that act in the nucleus,
e.g., steroids, thyroid hormone.
A
Mechanism of action of hormones:
Hormones released by endocrine glands and transported through the
bloodstream to tissues by binding to specific receptor and regulate target
tissue function.
Some hormones bind cell surface receptors,
e.g., insulin, growth hormone, prolactin.
Some hormones bind to intracellular receptors that act in the nucleus,
e.g., steroids, thyroid hormone.
6
Q
1- G-protein coupled receptors ( Seven-transmembrane domain receptors)
G-proteins are guanosine triphosphate (GTP)-binding proteins that couple
receptors to adjacent effector molecules.
Are used in the adenylate cyclase, Ca2+_ Calmodulin, and inositol 1,4,5-triphosphate
(IP3) second messenger system.
*Binding of ligand to the receptor activates G proteins, which in turn act on effectors
such as adenylyl cyclase and phospholipase C and in that way initiate production of
second messengers with resultant influences on cell organization, or transcription.
They have intrinsic GTPase activity
they have 3 subunits: α, β, and γ
The α subunit can bind GDP or GTP. When GDP is bound to α subunit, the G protein
is inactive. When GTP is bound, the G protein is active.
G proteins are either stimulatory (Gs) or inhibitory (Gi). Stimulatory or inhibitory activity
resides in the α subunits, which are accordingly called (αs) and (αi).
*Mediate actions of catecholamines, prostaglandins, ACTH, glucagons, parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), and others.
A
1- G-protein coupled receptors ( Seven-transmembrane domain receptors)
G-proteins are guanosine triphosphate (GTP)-binding proteins that couple
receptors to adjacent effector molecules.
Are used in the adenylate cyclase, Ca2+_ Calmodulin, and inositol 1,4,5-triphosphate
(IP3) second messenger system.
*Binding of ligand to the receptor activates G proteins, which in turn act on effectors
such as adenylyl cyclase and phospholipase C and in that way initiate production of
second messengers with resultant influences on cell organization, or transcription.
They have intrinsic GTPase activity
they have 3 subunits: α, β, and γ
The α subunit can bind GDP or GTP. When GDP is bound to α subunit, the G protein
is inactive. When GTP is bound, the G protein is active.
G proteins are either stimulatory (Gs) or inhibitory (Gi). Stimulatory or inhibitory activity
resides in the α subunits, which are accordingly called (αs) and (αi).
*Mediate actions of catecholamines, prostaglandins, ACTH, glucagons, parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), and others.
7
Q
G-protein coupled receptors ( Seven-transmembrane domain receptors)
They contain a surface-exposed amino-terminal domain followed by seven
transmembrane domains that span the lipid bilayer and a hydrophilic carboxyl
terminal domain that lies in the cytoplasm, these receptors are coupled to the
guanylyl nucleotide binding G proteins.
A
G-protein coupled receptors ( Seven-transmembrane domain receptors)
They contain a surface-exposed amino-terminal domain followed by seven
transmembrane domains that span the lipid bilayer and a hydrophilic carboxyl
terminal domain that lies in the cytoplasm, these receptors are coupled to the
guanylyl nucleotide binding G proteins.
8
Q
2- Growth factor receptors:
contains an amino terminal surface exposed ligand-binding domain, a single
membrane-spanning domain, and a carboxyl terminal catalytic domain.
Growth factor receptors, including those for insulin, IGF and EGF, possess tyrosine kinase activity. Ligand binding results to activation of tyrosine kinase, and
autophosphorylation.
A
2- Growth factor receptors:
contains an amino terminal surface exposed ligand-binding domain, a single
membrane-spanning domain, and a carboxyl terminal catalytic domain.
Growth factor receptors, including those for insulin, IGF and EGF, possess tyrosine kinase activity. Ligand binding results to activation of tyrosine kinase, and
autophosphorylation.
9
Q
3- Cytokine receptors: are part of a receptors that also mediate the actions of growth hormone (GH). This class contains a surface-exposed amino terminal domain that binds ligand, a single membrane-spanning domain, and a carboxyl terminal effector domain. GH receptors lack a tyrosine kinase domain, when GH bind to the receptor in the extracellular space (their mechanism of action is not perfectly understood ) but appears to involve the participation of signaling intermediates, like JAK2, a protein that possesses intrinsic tyrosine kinase activity. The association of JAK2 with the liganded GH receptor leads to change in JAK2 and activation of its tyrosine kinase catalytic activity. This, in turn, triggers downstream signaling events.
A
3- Cytokine receptors: are part of a receptors that also mediate the actions of growth hormone (GH). This class contains a surface-exposed amino terminal domain that binds ligand, a single membrane-spanning domain, and a carboxyl terminal effector domain. GH receptors lack a tyrosine kinase domain, when GH bind to the receptor in the extracellular space (their mechanism of action is not perfectly understood ) but appears to involve the participation of signaling intermediates, like JAK2, a protein that possesses intrinsic tyrosine kinase activity. The association of JAK2 with the liganded GH receptor leads to change in JAK2 and activation of its tyrosine kinase catalytic activity. This, in turn, triggers downstream signaling events.
10
Q
4- Ligand-regulated transporters (Guanylyl cyclase receptor)
can bind ligands and respond by opening the channel for ion flow.
In this case, the ion flux acts the second messenger, it increases nitric oxide synthases (NOS) , it leads to stimulation of soluble guanylyl cyclase (GC) activity. Subsequent elevations in cGMP activate cGMP -dependent protein kinase (PKG) and promote vasorelaxation.
A
4- Ligand-regulated transporters (Guanylyl cyclase receptor)
can bind ligands and respond by opening the channel for ion flow.
In this case, the ion flux acts the second messenger, it increases nitric oxide synthases (NOS) , it leads to stimulation of soluble guanylyl cyclase (GC) activity. Subsequent elevations in cGMP activate cGMP -dependent protein kinase (PKG) and promote vasorelaxation.
11
Q
Nuclear receptors
Nuclear receptors mediate actions of steroid hormones, vitamin D, thyroid hormones,
retinoids, fatty acids and bile acids.
Nuclear receptors control gene expression by binding to DNA response elements
in the promoters of target genes or to other transcription factors.
Nuclear receptor is composed of three domains: 1- The amino terminal domain is the most variable and mediates effects on transcription. 2- The DNA-binding domain 3-The carboxyl terminal domain is also well conserved and mediates ligand binding, dimerization, and effect on transcription.
A
Nuclear receptors
Nuclear receptors mediate actions of steroid hormones, vitamin D, thyroid hormones,
retinoids, fatty acids and bile acids.
Nuclear receptors control gene expression by binding to DNA response elements
in the promoters of target genes or to other transcription factors.
Nuclear receptor is composed of three domains: 1- The amino terminal domain is the most variable and mediates effects on transcription. 2- The DNA-binding domain 3-The carboxyl terminal domain is also well conserved and mediates ligand binding, dimerization, and effect on transcription.
12
Q
Steroid hormone and thyroid hormone mechanism:
1- Steroid or thyroid hormones diffuse across
the cell membrane of target cells and bind to
a cytosolic receptor and then to a nuclear receptor.
Binding to the nuclear receptor causes a
conformational change in the receptor,
which exposes a DNA-binding domain.
2- In the nucleus, the DNA-binding domain on
the receptor interacts with the hormone
regulatory elements of specific DNA.
Transcription is initiated and results in the
production of new mRNA.
3- mRNA is translated in the cytoplasm and
results in the production of specific proteins
that have physiologic actions.
A
Steroid hormone and thyroid hormone mechanism:
1- Steroid or thyroid hormones diffuse across
the cell membrane of target cells and bind to
a cytosolic receptor and then to a nuclear receptor.
Binding to the nuclear receptor causes a
conformational change in the receptor,
which exposes a DNA-binding domain.
2- In the nucleus, the DNA-binding domain on
the receptor interacts with the hormone
regulatory elements of specific DNA.
Transcription is initiated and results in the
production of new mRNA.
3- mRNA is translated in the cytoplasm and
results in the production of specific proteins
that have physiologic actions.
13
Q
Chemical substance which is secreted by endocrine gland which carries some signal to target cell.
A
Chemical substance which is secreted by endocrine gland which carries some signal to target cell.
14
Q
Endocrine
Secreted into blood stream
A
Endocrine
Secreted into blood stream
15
Q
Hormone requires specific receptor
The type of receptor depends on the type of hormone
When hormone binds to its receptor it leads to stimulation of intracellular molecules in target cell
After activation of molecules then that target cell shows physiologic reaction to the hormone
A
Hormone requires specific receptor
The type of receptor depends on the type of hormone
When hormone binds to its receptor it leads to stimulation of intracellular molecules in target cell
After activation of molecules then that target cell shows physiologic reaction to the hormone
16
Q
In general there are two groups of hormones
Protein hormones(amino acid/poly peptide hormones) which binds to cell surface receptor
On cell membrane
Protein can not pass through cell membrane since the structure of cell membrane is
A
In general there are two groups of hormones
Protein hormones(amino acid/poly peptide hormones) which binds to cell surface receptor
On cell membrane
Protein can not pass through cell membrane since the structure of cell membrane is
17
Q
lipid bilayer Hormones which bind to nuclear receptor Located inside the nucleus Steroid hormones Precursor is cholesterol Aldosterone and cortisol Sex hormones(testosterone, androgen, progesterone, estrogen) Vitamin D Precursor is cholesterol T3 and T4 Precursor is iodine These can easily pass through cell membrane and they bind into the nuclear receptor
A
lipid bilayer Hormones which bind to nuclear receptor Located inside the nucleus Steroid hormones Precursor is cholesterol Aldosterone and cortisol Sex hormones(testosterone, androgen, progesterone, estrogen) Vitamin D Precursor is cholesterol T3 and T4 Precursor is iodine These can easily pass through cell membrane and they bind into the nuclear receptor
18
Q
Different types of hormones
Exocrine glands
Sweat glands, salivary glands
Anything with a duct that open into a cavity and the contents are released into it
Endocrine
Into blood stream
Paracrine hormones
First hormone controls/regulates neighboring cell hormone secretion
Somatostatin in GI tract inhibits other hormone gastric secretion
In hypothalamus inhibits growth hormone secretion
(clinical point) synthetic somatostatin is used for treatment of gigantism because it blocks the growth hormone
Autocrine hormones
Hormone controls its own secretion
Insulin gives itself feedback
A
Different types of hormones
Exocrine glands
Sweat glands, salivary glands
Anything with a duct that open into a cavity and the contents are released into it
Endocrine
Into blood stream
Paracrine hormones
First hormone controls/regulates neighboring cell hormone secretion
Somatostatin in GI tract inhibits other hormone gastric secretion
In hypothalamus inhibits growth hormone secretion
(clinical point) synthetic somatostatin is used for treatment of gigantism because it blocks the growth hormone
Autocrine hormones
Hormone controls its own secretion
Insulin gives itself feedback
19
Q
(clinical point) synthetic somatostatin is used for treatment of gigantism because it blocks the growth hormone
A
(clinical point) synthetic somatostatin is used for treatment of gigantism because it blocks the growth hormone
20
Q
(hormone interactions)
Sometimes two different hormones have similar functions
Glucagon and cortisol maintain the blood glucose level but different hormones
Sometimes some hormones can stimulate or inhibit other secretions
Prolactin suppresses the sex hormones to prevent menstruation during pregnancy
Antagonist
When hormone or synthetic hormone or drug recognizes natural hormone receptor then it binds to that receptor which blocks the natural hormone effect
Propranolol is beta 1 blocker
Antagonist to beta 1
A
(hormone interactions)
Sometimes two different hormones have similar functions
Glucagon and cortisol maintain the blood glucose level but different hormones
Sometimes some hormones can stimulate or inhibit other secretions
Prolactin suppresses the sex hormones to prevent menstruation during pregnancy
Antagonist
When hormone or synthetic hormone or drug recognizes natural hormone receptor then it binds to that receptor which blocks the natural hormone effect
Propranolol is beta 1 blocker
Antagonist to beta 1
21
Q
Agonist
Synthetic hormone recognizes the natural hormone receptor and acts as the hormone
Synthetic growth hormone replacement for dwarfism
Replace the growth hormone to encourage growth
A
Agonist
Synthetic hormone recognizes the natural hormone receptor and acts as the hormone
Synthetic growth hormone replacement for dwarfism
Replace the growth hormone to encourage growth
22
Q
Slide 6 mechanism of action
- When a ligand or hormone binds to its specific receptor
- Activates intracellular molecules
o Effector – first activated, mostly is g protein(alpha, beta and gamma subunits)
- After activation of effector then second messenger is activated
o Activation of some enzymes
o Phospholipids C
- Sometimes it leads to inhibition of second messenger
- This leads to activation of intracellular energy(CAMP – cyclic adenosine monophosphate)
- The target cell shows reaction to that hormone
- Intracellular and nuclear can be interchanged in wording
A
Slide 6 mechanism of action
- When a ligand or hormone binds to its specific receptor
- Activates intracellular molecules
o Effector – first activated, mostly is g protein(alpha, beta and gamma subunits)
- After activation of effector then second messenger is activated
o Activation of some enzymes
o Phospholipids C
- Sometimes it leads to inhibition of second messenger
- This leads to activation of intracellular energy(CAMP – cyclic adenosine monophosphate)
- The target cell shows reaction to that hormone
- Intracellular and nuclear can be interchanged in wording
23
Q
Slide 7 - For test o Know the underlined o Adenylate cyclase to GTPase activity - The cell surface receptors have 4 types of receptors for proteins o G protein coupled receptors o Growth factor receptor o Cytokine receptors o Ligand-regulated transporters - For test o Know catecholamines Same as adrenaline and noradrenaline
A
Slide 7 - For test o Know the underlined o Adenylate cyclase to GTPase activity - The cell surface receptors have 4 types of receptors for proteins o G protein coupled receptors o Growth factor receptor o Cytokine receptors o Ligand-regulated transporters - For test o Know catecholamines Same as adrenaline and noradrenaline
24
Q
Slide 9
- Insulin, IGF, and EGF
- The second messenger for growth factor is Tyrosine kinase
- Insulin can bind the growth factor receptor
A
Slide 9
- Insulin, IGF, and EGF
- The second messenger for growth factor is Tyrosine kinase
- Insulin can bind the growth factor receptor
25
Slide 11
- Cytokine receptors are for growth factors
- JAK2 and tyrosine kinase
Slide 11
- Cytokine receptors are for growth factors
- JAK2 and tyrosine kinase
26
Slide 12
- Nitric oxide and ANP(atrial natriotic peptide) bind
o ANP is vasorelaxator which decreases blood pressure and is active when blood pressure is high
Slide 12
- Nitric oxide and ANP(atrial natriotic peptide) bind
o ANP is vasorelaxator which decreases blood pressure and is active when blood pressure is high
27
Slide 13
Nuclear receptor is not part of the 4 above
- One side is for ligand binding site and the other part is for the DNA binding site
- Steroid hormones, vitamin D
Slide 13
Nuclear receptor is not part of the 4 above
- One side is for ligand binding site and the other part is for the DNA binding site
- Steroid hormones, vitamin D
28
o (clinical point) any deficiency or over production of precursor or hormone again leads to hormonal disorder
Deficiency of cholesterol leads to deficiency of sex hormones = infertility
Deficiency of testosterone leads to depression(controls mood)
o (clinical point) any deficiency or over production of precursor or hormone again leads to hormonal disorder
Deficiency of cholesterol leads to deficiency of sex hormones = infertility
Deficiency of testosterone leads to depression(controls mood)
29
o (clinical point) any modification or change/mutation to receptor structure leads to hormonal disorder such as
Type 2 diabetes
o (clinical point) any modification or change/mutation to receptor structure leads to hormonal disorder such as
Type 2 diabetes
30
The differences between cell surface receptor and nuclear receptor hormones
- Cell surface = protein
- Nuclear = steroid hormones
- Protein hormones should bind to cell membrane receptor but steroid hormone should bind to nuclear receptor hormone
- Steroid hormones need a carrier protein which transports the hormone to the nucleus but protein hormones freely circulate in blood stream and don’t need a carrier protein
- Duration of action for steroid hormone is longer than protein hormone because
o Needs to dissociate from its carrier protein which takes some time
- Protein hormones are hydrophilic(lipophobic) and can not pass through the cell membrane
o Steroid hormones are lipophilic and can pass through the cell membrane
- Precursors
o Protein hormone – amino acid
o Steroid – cholesterol
o (clinical point) any modification or change/mutation to receptor structure leads to hormonal disorder such as
Type 2 diabetes
o (clinical point) any deficiency or over production of precursor or hormone again leads to hormonal disorder
Deficiency of cholesterol leads to deficiency of sex hormones = infertility
Deficiency of testosterone leads to depression(controls mood)
The differences between cell surface receptor and nuclear receptor hormones
- Cell surface = protein
- Nuclear = steroid hormones
- Protein hormones should bind to cell membrane receptor but steroid hormone should bind to nuclear receptor hormone
- Steroid hormones need a carrier protein which transports the hormone to the nucleus but protein hormones freely circulate in blood stream and don’t need a carrier protein
- Duration of action for steroid hormone is longer than protein hormone because
o Needs to dissociate from its carrier protein which takes some time
- Protein hormones are hydrophilic(lipophobic) and can not pass through the cell membrane
o Steroid hormones are lipophilic and can pass through the cell membrane
- Precursors
o Protein hormone – amino acid
o Steroid – cholesterol
o (clinical point) any modification or change/mutation to receptor structure leads to hormonal disorder such as
Type 2 diabetes
o (clinical point) any deficiency or over production of precursor or hormone again leads to hormonal disorder
Deficiency of cholesterol leads to deficiency of sex hormones = infertility
Deficiency of testosterone leads to depression(controls mood)
31
First signal comes from hypothalamus
| Second signal the hypophyseal gland
First signal comes from hypothalamus
| Second signal the hypophyseal gland
32
The pituitary gland has 3 lobes
Anterior, posterior, and inter media lobe
Hypothalamal-pituitary portal system connects anterior and posterior
The pituitary gland has 3 lobes
Anterior, posterior, and inter media lobe
Hypothalamal-pituitary portal system connects anterior and posterior
33
Hypothalamus connects to posterior pituitary is by axon not blood vessel
The embryonic origin of posterior lobe is from the ectoderm which gives signals to CNS and PNS
This is why it is axon instead of blood vessel based like anterior pituitary
Hypothalamus connects to posterior pituitary is by axon not blood vessel
The embryonic origin of posterior lobe is from the ectoderm which gives signals to CNS and PNS
This is why it is axon instead of blood vessel based like anterior pituitary
34
```
Hypothalamus contains some nuclei
These nuclei secrete type types of hormones
- Releasing hormones and inhibit releasing hormone
o RH and IRH
o R from hypothalamus
releasing
o S from anterior pituitary lobe
Stimulating
```
```
Hypothalamus contains some nuclei
These nuclei secrete type types of hormones
- Releasing hormones and inhibit releasing hormone
o RH and IRH
o R from hypothalamus
releasing
o S from anterior pituitary lobe
Stimulating
```
35
Hypothalmus controls
- Endocrine system
- Appetite
- Memory
- Learning
- Emotional sexual behaviors
- Partially sympathetic and parasympathetic
- Body temperature
Hypothalmus controls
- Endocrine system
- Appetite
- Memory
- Learning
- Emotional sexual behaviors
- Partially sympathetic and parasympathetic
- Body temperature
36
(clinical point)
25 year old male has tumor in hypothalamic nuclei what signs/symptoms if the surgeon can not remove the tumor?
Obesity
Sleep disorder
(clinical point)
25 year old male has tumor in hypothalamic nuclei what signs/symptoms if the surgeon can not remove the tumor?
Obesity
Sleep disorder
37
Connections of the Hypothalamus with the Hypophysis cerebri:
The hypothalamus is connected to the hypophysis cerebri (pituitary gland) by two ways:
1- nerve fibers from the supraoptic and paraventricular nuclei to posterior pituitary lobe.
2- long and short portal blood vessels connecting sinusoids in the median eminence and
infundibulum with capillary plexus in the anterior lobe of the hypophysis.
These pathways enables the hypothalamus to influence the endocrine glands activities.
Connections of the Hypothalamus with the Hypophysis cerebri:
The hypothalamus is connected to the hypophysis cerebri (pituitary gland) by two ways:
1- nerve fibers from the supraoptic and paraventricular nuclei to posterior pituitary lobe.
2- long and short portal blood vessels connecting sinusoids in the median eminence and
infundibulum with capillary plexus in the anterior lobe of the hypophysis.
These pathways enables the hypothalamus to influence the endocrine glands activities.
38
Hormones of the anterior lobe of the pituitary
```
Growth hormone (GH)
Adrenocorticotropic hormone (ACTH),
Follicle- Stimulating hormone (FSH),
Luteinizing hormone (LH),
Thyroid- Stimulating hormone (TSH),
Prolactin (PL)
```
Hormones of the
posterior lobe of the pituitary
1- Vasopressin or Antidiuretic hormone (ADH)
2- Oxytocin
Hormones of the anterior lobe of the pituitary
```
Growth hormone (GH)
Adrenocorticotropic hormone (ACTH),
Follicle- Stimulating hormone (FSH),
Luteinizing hormone (LH),
Thyroid- Stimulating hormone (TSH),
Prolactin (PL)
```
Hormones of the
posterior lobe of the pituitary
1- Vasopressin or Antidiuretic hormone (ADH)
2- Oxytocin
39
Adrenal gland
It is located in the retroperitoneum above or medial to the upper poles of the kidneys.
It has two parts cortex (outer layer) and medulla , 90% is cortex and 10% is the inner medulla.
Adrenal gland
It is located in the retroperitoneum above or medial to the upper poles of the kidneys.
It has two parts cortex (outer layer) and medulla , 90% is cortex and 10% is the inner medulla.
40
Structure of the adrenal cortex
About 90% of the adrenal gland is composed of the cortex.
It consists of three layers (zones).
Structure of the adrenal cortex
About 90% of the adrenal gland is composed of the cortex.
It consists of three layers (zones).
41
1- Synthesis of adrenocortical hormones
The cortex has 3 layers: They produce steroid hormones from cholesterol
as a common precursor.
Zona glomerulosa: produces mineralocorticoids (aldosterone)
Zona fasciculata: produces mostly glucocorticoids (cortisol)
Zona reticulata: produces sex hormones (mostly androgens, dehydroepiandro-
-sterone and androstenedione).
*Adrenal cortex is regulated by pituitary hormone ACTH.
1- Synthesis of adrenocortical hormones
The cortex has 3 layers: They produce steroid hormones from cholesterol
as a common precursor.
Zona glomerulosa: produces mineralocorticoids (aldosterone)
Zona fasciculata: produces mostly glucocorticoids (cortisol)
Zona reticulata: produces sex hormones (mostly androgens, dehydroepiandro-
-sterone and androstenedione).
*Adrenal cortex is regulated by pituitary hormone ACTH.
42
Aldosterone secretion
Is under tonic control by ACTH, but is separately regulated by the
renin-angiotensin system and the potassium.
Renin- angiotensin- aldosterone system:
A- decreases in blood volume cause a decrease in renal perfusion pressure,
which in turn increases renin secretion.
-Renin, an enzyme, catalyzes the conversion of angiotensinogen to angiotensin I.
-Angiotensin I is converted to angiotensin II by angiotensin-converting
enzyme (ACE).
B- Angiotensin II acts on the zona glomerulosa of the adrenal cortex to increase
the conversion of corticosterone to aldosterone.
C- Aldosterone increases renal Na+ reabsorbtion, thereby restoring extracellular
fluid (CSF) volume and blood volume to normal.
D- Hyperkalemia increases aldosterone secretion. Aldosterone increases renal
K+ secretion, restoring blood [K+] to normal.
Aldosterone secretion
Is under tonic control by ACTH, but is separately regulated by the
renin-angiotensin system and the potassium.
Renin- angiotensin- aldosterone system:
A- decreases in blood volume cause a decrease in renal perfusion pressure,
which in turn increases renin secretion.
-Renin, an enzyme, catalyzes the conversion of angiotensinogen to angiotensin I.
-Angiotensin I is converted to angiotensin II by angiotensin-converting
enzyme (ACE).
B- Angiotensin II acts on the zona glomerulosa of the adrenal cortex to increase
the conversion of corticosterone to aldosterone.
C- Aldosterone increases renal Na+ reabsorbtion, thereby restoring extracellular
fluid (CSF) volume and blood volume to normal.
D- Hyperkalemia increases aldosterone secretion. Aldosterone increases renal
K+ secretion, restoring blood [K+] to normal.
43
Actions of mineralocorticoids (aldosterone)
1- increase renal Na+ reabsorption (action on the principal cells of the late
distal tubule and collecting duct).
2- increase renal K+ secretion (action on the principal cells of the late
distal tubule and collecting duct).
3- increase renal H+ secretion (action on the intercalated cells of the late
distal tubule and collecting duct).
Actions of mineralocorticoids (aldosterone)
1- increase renal Na+ reabsorption (action on the principal cells of the late
distal tubule and collecting duct).
2- increase renal K+ secretion (action on the principal cells of the late
distal tubule and collecting duct).
3- increase renal H+ secretion (action on the intercalated cells of the late
distal tubule and collecting duct).
44
Actions of Glucocorticoids (cortisol)
The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism. In the fasted state, cortisol stimulates several processes that collectively serve to increase and maintain normal concentrations of glucose in blood. These effects include:
1- Stimulation of gluconeogenesis, glucocorticoids increase gluconeogenesis by the following mechanisms:
A- increase in protein catabolizm
B- They decrease glucose utilization and insulin sensitivity of adipose tissue.
C- They increase lipolysis, which provides more glycerol to the liver for
gluconeogenesis. Also, the fatty acids released by lipolysis are used for production of energy in tissues like muscle.
2- Anti-inflammatory effects
Actions of Glucocorticoids (cortisol)
The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism. In the fasted state, cortisol stimulates several processes that collectively serve to increase and maintain normal concentrations of glucose in blood. These effects include:
1- Stimulation of gluconeogenesis, glucocorticoids increase gluconeogenesis by the following mechanisms:
A- increase in protein catabolizm
B- They decrease glucose utilization and insulin sensitivity of adipose tissue.
C- They increase lipolysis, which provides more glycerol to the liver for
gluconeogenesis. Also, the fatty acids released by lipolysis are used for production of energy in tissues like muscle.
2- Anti-inflammatory effects
45
Pathophysiology of the adrenal cortex
A- Adrenocortical insufficiency
1- primary adrenocortical insufficiency, Addison’s disease
2- secondary adrenocortical insufficiency
B- Adrenocortical excess: Cushing’s syndrome
C- Hyperaldosteronism: Conn’s syndrome
Pathophysiology of the adrenal cortex
A- Adrenocortical insufficiency
1- primary adrenocortical insufficiency, Addison’s disease
2- secondary adrenocortical insufficiency
B- Adrenocortical excess: Cushing’s syndrome
C- Hyperaldosteronism: Conn’s syndrome
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Adrenal medulla
Hormones of the adrenal medulla
Epinephrine is synthesized mainly in the adrenal medulla, whereas Norepinephrine is found not only in the adrenal medulla but also in the central nervous system and in the peripheral sympathetic nerves. Dopamine, the precursor of norepinephrine, is found in the adrenal medulla and in noradrenergic neurons. Dopamine is also found in specialized mast cells.
Synthesis and Secretion of Catecholamines
Synthesis of catecholamines begins with the amino acid tyrosine, which is taken up by chromaffin cells in the medulla and converted to norepinephrine and epinephrine through the following steps:
Adrenal medulla
Hormones of the adrenal medulla
Epinephrine is synthesized mainly in the adrenal medulla, whereas Norepinephrine is found not only in the adrenal medulla but also in the central nervous system and in the peripheral sympathetic nerves. Dopamine, the precursor of norepinephrine, is found in the adrenal medulla and in noradrenergic neurons. Dopamine is also found in specialized mast cells.
Synthesis and Secretion of Catecholamines
Synthesis of catecholamines begins with the amino acid tyrosine, which is taken up by chromaffin cells in the medulla and converted to norepinephrine and epinephrine through the following steps:
47
Thyroid gland
The thyroid gland produces two related hormones, Thyroxine (T4) and triiodothyronine (T3). Acting through nuclear receptors, these hormones play a critical role in cell differentiation during development and help maintain thermogenic and metabolic homeostasis in the adult.
Thyroid gland
The thyroid gland produces two related hormones, Thyroxine (T4) and triiodothyronine (T3). Acting through nuclear receptors, these hormones play a critical role in cell differentiation during development and help maintain thermogenic and metabolic homeostasis in the adult.
48
Structure of thyroid gland
On microscopic examination, the thyroid gland contains a series of follicles, the follicles contain a pink-staining material called “colloid” and are surrounded by single layer of thyroid epithelium. Colloid, a proteinaceous fluid that contains large amounts of thyroglobulin, the protein precursor of thyroid hormones. The thyroid follicular cells are polarized- the basolateral surface is apposed to the bloodstream and an apical surface faces the follicular lumen. Increased demand for thyroid hormone, usually signaled by thyroid-stimulating hormone (TSH) binding to its receptor on the basolateral surface of the follicular cells, leads to thyroglobulin reabsorption from the follicular lumen and proteolysis within the cell to yield thyroid hormones for secretion into the bloodstream.
Structure of thyroid gland
On microscopic examination, the thyroid gland contains a series of follicles, the follicles contain a pink-staining material called “colloid” and are surrounded by single layer of thyroid epithelium. Colloid, a proteinaceous fluid that contains large amounts of thyroglobulin, the protein precursor of thyroid hormones. The thyroid follicular cells are polarized- the basolateral surface is apposed to the bloodstream and an apical surface faces the follicular lumen. Increased demand for thyroid hormone, usually signaled by thyroid-stimulating hormone (TSH) binding to its receptor on the basolateral surface of the follicular cells, leads to thyroglobulin reabsorption from the follicular lumen and proteolysis within the cell to yield thyroid hormones for secretion into the bloodstream.
49
Synthesis of Thyroid hormones:
1- The iodide (I-) pump
Is present in the thyroid follicular epithelial cells.
actively transports I- into the thyroid follicular cells for subsequent incorporation
into thyroid hormones.
Synthesis of Thyroid hormones:
1- The iodide (I-) pump
Is present in the thyroid follicular epithelial cells.
actively transports I- into the thyroid follicular cells for subsequent incorporation
into thyroid hormones.
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Synthesis of Thyroid hormones:
2- Oxidation of I- to I2
Is catalyzed by a peroxidase enzyme in the follicular cell membrane.
I2 is the reactive form, which will be organofied by combination with tyrosine
on thyroglobulin.
- The same peroxidase enzyme catalyses the remaining organification and
coupling reactions involved in the synthesis of thyroid hormones.
Synthesis of Thyroid hormones:
2- Oxidation of I- to I2
Is catalyzed by a peroxidase enzyme in the follicular cell membrane.
I2 is the reactive form, which will be organofied by combination with tyrosine
on thyroglobulin.
- The same peroxidase enzyme catalyses the remaining organification and
coupling reactions involved in the synthesis of thyroid hormones.
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Synthesis of Thyroid hormones:
3- Organification of I2
Tyrosine is incorporated into thyroglobulin on the ribosomes of the thyroid
follicular cells.
Thyroglobulin is then packaged in secretory vesicles on the Golgi apparatus
and extruded into follicular lumen.
At the junction of the follicular cells and the follicular lumen, tyrosine residues of
thyroglobulin react with I2 to form monoiodotyrosine (MIT) and diiodotyrosine (DIT).
Synthesis of Thyroid hormones:
3- Organification of I2
Tyrosine is incorporated into thyroglobulin on the ribosomes of the thyroid
follicular cells.
Thyroglobulin is then packaged in secretory vesicles on the Golgi apparatus
and extruded into follicular lumen.
At the junction of the follicular cells and the follicular lumen, tyrosine residues of
thyroglobulin react with I2 to form monoiodotyrosine (MIT) and diiodotyrosine (DIT).
52
Synthesis of Thyroid hormones:
4- Coupling of MIT and DIT
While MIT and DIT are attached to thyroglobulin, two coupling reactions occur:
A- When two molecules of DIT combine, thyroxine (T4) is formed.
B- When one molecule of DIT combines with one molecule of MIT, triiodothyronine
(T3) is formed.
More T4 than T3 is synthesized, although T3 is more active.
5- Iodinated thyroglobulin
Is stored in the follicular lumen until the thyroid gland is stimulated to secrete
thyroid hormones.
Synthesis of Thyroid hormones:
4- Coupling of MIT and DIT
While MIT and DIT are attached to thyroglobulin, two coupling reactions occur:
A- When two molecules of DIT combine, thyroxine (T4) is formed.
B- When one molecule of DIT combines with one molecule of MIT, triiodothyronine
(T3) is formed.
More T4 than T3 is synthesized, although T3 is more active.
5- Iodinated thyroglobulin
Is stored in the follicular lumen until the thyroid gland is stimulated to secrete
thyroid hormones.
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Regulation of thyroid hormone secretion
1- Hypothalamic-pituitary control- TRH and TSH
A- TRH is secreted by the hypothalamus and stimulates the secretion of TSH
by the anterior pituitary.
B- TSH increases both synthesis and secretion of thyroid hormones by the
follicular cells via an adenylate cyclase- cAMP mechanism.
Chronic elevation of TSH causes hypertrophy of the thyroid gland.
C- T3 down-regulates TRH receptors in
the anterior pituitary and thereby
inhibits TSH secretion.
Regulation of thyroid hormone secretion
1- Hypothalamic-pituitary control- TRH and TSH
A- TRH is secreted by the hypothalamus and stimulates the secretion of TSH
by the anterior pituitary.
B- TSH increases both synthesis and secretion of thyroid hormones by the
follicular cells via an adenylate cyclase- cAMP mechanism.
Chronic elevation of TSH causes hypertrophy of the thyroid gland.
C- T3 down-regulates TRH receptors in
the anterior pituitary and thereby
inhibits TSH secretion.
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Thyroid hormones in the blood
About 99,9% of the circulating T4 and 99,5%
of the circulating T3 are bound to plasma
proteins, primarily to thyroxine binding globulin (TBG).
Binding to plasma proteins ensures a circulating
reserve - free T4 and T3 are readily excreted
by the kidneys.
Thyroid hormones in the blood
About 99,9% of the circulating T4 and 99,5%
of the circulating T3 are bound to plasma
proteins, primarily to thyroxine binding globulin (TBG).
Binding to plasma proteins ensures a circulating
reserve - free T4 and T3 are readily excreted
by the kidneys.
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Actions of thyroid hormone
T3 is three to four times more potent than T4. The target tissues convert T4 to T3.
1. Growth
-Thyroid hormones act synergistically with growth hormone and somatomedins to
promote bone formation.
-Thyroid hormones stimulate bone maturation as a result of ossification and fusion
of the growth plates.
Actions of thyroid hormone
T3 is three to four times more potent than T4. The target tissues convert T4 to T3.
1. Growth
-Thyroid hormones act synergistically with growth hormone and somatomedins to
promote bone formation.
-Thyroid hormones stimulate bone maturation as a result of ossification and fusion
of the growth plates.
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Actions of thyroid hormone (continued)
2. Central nervous system (CNS)
Perinatal period
- Maturation of the CNS is absolutely dependent on thyroid hormone in the perinatal period.
- Thyroid hormone deficiency causes irreversible mental retardation.
b. Adulthood
- Hyperthyroidism causes hyperexcitability and irritability.
- Hypothyroidism causes slowed speech, somnolence, impaired memory, and decreased mental capacity.
3. Autonomic nervous system
-Thyroid hormone has many of the same actions of sympathetic stimulation (it
Up-regulates β1-adrenergic receptors in the heart).
4. Basal metabolic rate (BMR)
-O2 consumption and BMR are increased by thyroid hormone in all tissues except the brain, gonads, and spleen. The resulting increase in heat production underlies the
role of thyroid hormone in temperature regulation.
Actions of thyroid hormone (continued)
2. Central nervous system (CNS)
Perinatal period
- Maturation of the CNS is absolutely dependent on thyroid hormone in the perinatal period.
- Thyroid hormone deficiency causes irreversible mental retardation.
b. Adulthood
- Hyperthyroidism causes hyperexcitability and irritability.
- Hypothyroidism causes slowed speech, somnolence, impaired memory, and decreased mental capacity.
3. Autonomic nervous system
-Thyroid hormone has many of the same actions of sympathetic stimulation (it
Up-regulates β1-adrenergic receptors in the heart).
4. Basal metabolic rate (BMR)
-O2 consumption and BMR are increased by thyroid hormone in all tissues except the brain, gonads, and spleen. The resulting increase in heat production underlies the
role of thyroid hormone in temperature regulation.
57
Actions of thyroid hormone (continued)
5. Cardiovascular and respiratory systems
-Effects of thyroid hormone on cardiac output and ventilation rate combine to ensure
that more O2 is delivered to the tissues.
a. increase heart rate and stroke volume are increased, leading to cardiac output.
b. increases ventilation rate.
6. Metabolic effects
Overall metabolism is increased to meet the demands for substrate associated
with the increased rate of O2 consumption.
a. Increases glucose absorption from the gastrointestinal tract
b. Increase glycogenolysis, gluconeogenesis, and glucose oxidation
c. Increases lipolysis
d. Increases protein synthesis and degradation. The overall effect is catabolic.
Actions of thyroid hormone (continued)
5. Cardiovascular and respiratory systems
-Effects of thyroid hormone on cardiac output and ventilation rate combine to ensure
that more O2 is delivered to the tissues.
a. increase heart rate and stroke volume are increased, leading to cardiac output.
b. increases ventilation rate.
6. Metabolic effects
Overall metabolism is increased to meet the demands for substrate associated
with the increased rate of O2 consumption.
a. Increases glucose absorption from the gastrointestinal tract
b. Increase glycogenolysis, gluconeogenesis, and glucose oxidation
c. Increases lipolysis
d. Increases protein synthesis and degradation. The overall effect is catabolic.
58
Parathyroid gland
The parathyroid glands are four pea-sized glands located on the thyroid gland in the neck. The parathyroid glands regulate serum calcium and phosphorus levels through the secretion of parathyroid hormone (PTH), which raises serum calcium levels while lowering the serum phosphorus concentration. The regulation of PTH secretion occurs through a negative feedback loop in which calcium-sensing receptors on the membranes of parathyroid cells trigger decreased PTH production as serum calcium concentrations rise.
Parathyroid gland
The parathyroid glands are four pea-sized glands located on the thyroid gland in the neck. The parathyroid glands regulate serum calcium and phosphorus levels through the secretion of parathyroid hormone (PTH), which raises serum calcium levels while lowering the serum phosphorus concentration. The regulation of PTH secretion occurs through a negative feedback loop in which calcium-sensing receptors on the membranes of parathyroid cells trigger decreased PTH production as serum calcium concentrations rise.
59
Parathyroid hormone (PTH) is synthesized and secreted by the chief cells of the parathyroid glands.
PTH is the major hormone for the regulation of serum [Ca2+]
Parathyroid hormone (PTH) is synthesized and secreted by the chief cells of the parathyroid glands.
PTH is the major hormone for the regulation of serum [Ca2+]
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Secretion of PTH
Is controlled by serum [Ca2+] through negative feedback.
Decreased serum [Ca2+] increases PTH secretion.
Mild decreases in serum [Mg2+] stimulates PTH secretion
Severe decreases in serum [Mg2+] inhibits PTH secretion and produce
symptoms of hypoparathyroidism (e.g., hypocalcemia).
The second messenger for PTH secretion is cAMP.
Secretion of PTH
Is controlled by serum [Ca2+] through negative feedback.
Decreased serum [Ca2+] increases PTH secretion.
Mild decreases in serum [Mg2+] stimulates PTH secretion
Severe decreases in serum [Mg2+] inhibits PTH secretion and produce
symptoms of hypoparathyroidism (e.g., hypocalcemia).
The second messenger for PTH secretion is cAMP.
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Actions of PTH
PTH increases serum [Ca2+] and decreases serum [phosphate].
The 2nd messenger for PTH actions on its target cells is cAMP.
1- PTH increases bone resorption
This brings both Ca2+ and phosphate from bone minerals to ECF.
Alone, this effect on bone would not increase serum ionized [Ca2+] because
phosphate complexes Ca2+.
- Resorption of the organic matrix of the bone is reflected in increased
hydroxyproline excretion.
Actions of PTH
PTH increases serum [Ca2+] and decreases serum [phosphate].
The 2nd messenger for PTH actions on its target cells is cAMP.
1- PTH increases bone resorption
This brings both Ca2+ and phosphate from bone minerals to ECF.
Alone, this effect on bone would not increase serum ionized [Ca2+] because
phosphate complexes Ca2+.
- Resorption of the organic matrix of the bone is reflected in increased
hydroxyproline excretion.
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Actions of PTH (continued)
2- PTH inhibits renal phosphate resorption in the proximal tubules, and
therefore, increases phosphate excretion (phosphaturic effect).
As a result, the phosphate resorbed from bone is excreted in the urine, allowing
the serum [Ca2+] to increase.
cAMP generated as a result of the action of PTH on the proximal tubule is
excreted in the urine (urinary cAMP).
3- PTH increases renal Ca2+ reabsorption in the distal tubule, which also
increases the serum [Ca2+].
4- PTH increases intestinal Ca2+ absorption indirectly by stimulating the
production of 1, 25-dihydroxycholecalciferol in the kidney.
Actions of PTH (continued)
2- PTH inhibits renal phosphate resorption in the proximal tubules, and
therefore, increases phosphate excretion (phosphaturic effect).
As a result, the phosphate resorbed from bone is excreted in the urine, allowing
the serum [Ca2+] to increase.
cAMP generated as a result of the action of PTH on the proximal tubule is
excreted in the urine (urinary cAMP).
3- PTH increases renal Ca2+ reabsorption in the distal tubule, which also
increases the serum [Ca2+].
4- PTH increases intestinal Ca2+ absorption indirectly by stimulating the
production of 1, 25-dihydroxycholecalciferol in the kidney.
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Organization of Endocrine Pancreas
The islets of Langerhans contain 3 major cell types.
Alpha cells: located in the outer rim of islet, secrete glucagon
Beta cells: located in the central part of the islet, secrete insulin.
Delta cells: are intermixed and secrete somatostatin and gastrin.
There are gap junctions which link beta cells to each other, alpha cells to
each other and beta cells to alpha cells for rapid communication.
Organization of Endocrine Pancreas
The islets of Langerhans contain 3 major cell types.
Alpha cells: located in the outer rim of islet, secrete glucagon
Beta cells: located in the central part of the islet, secrete insulin.
Delta cells: are intermixed and secrete somatostatin and gastrin.
There are gap junctions which link beta cells to each other, alpha cells to
each other and beta cells to alpha cells for rapid communication.
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Exocrine – acini
Digestive secretions
```
Endocrine
Islets of Langerhans
No external pathway
products go to the blood stream
Beta cells – 60% - insulin
Alpha cells – 25% - glucagon
Delta cells – 10% - somatostatin
Other cells and products such as PP cells that secrete pancreatic polypeptide
```
Exocrine – acini
Digestive secretions
```
Endocrine
Islets of Langerhans
No external pathway
products go to the blood stream
Beta cells – 60% - insulin
Alpha cells – 25% - glucagon
Delta cells – 10% - somatostatin
Other cells and products such as PP cells that secrete pancreatic polypeptide
```
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Glucagon
*Regulation of glucagon secretion:
The major factor controlling the glucagon regulation is the
blood glucose concentration
*Actions of glucagon:
Glucagon acts on the liver and adipose tissue.
The 2nd messenger system for glucagon is cAMP
Glucagon increases the blood glucose concentration.
(Very potent – 1 g/kg can elevate blood glucose 20 mg/dl in 20 min)
It increases glycogenolysis and prevents recycling of glucose into glycogen
It increases gluconeogenesis
It increases blood fatty acid and ketoacid concentration.
It increases lipolysis,
Glucagon increases urea Production, Amino acids are used for gluconeogenesis
(stimulated by glucagon), and the resulting amino group are incorporated into urea.
Glucagon
*Regulation of glucagon secretion:
The major factor controlling the glucagon regulation is the
blood glucose concentration
*Actions of glucagon:
Glucagon acts on the liver and adipose tissue.
The 2nd messenger system for glucagon is cAMP
Glucagon increases the blood glucose concentration.
(Very potent – 1 g/kg can elevate blood glucose 20 mg/dl in 20 min)
It increases glycogenolysis and prevents recycling of glucose into glycogen
It increases gluconeogenesis
It increases blood fatty acid and ketoacid concentration.
It increases lipolysis,
Glucagon increases urea Production, Amino acids are used for gluconeogenesis
(stimulated by glucagon), and the resulting amino group are incorporated into urea.
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Actions of insulin
Insulin acts on liver, adipose tissue and muscle
1- insulin decreases the blood glucose concentration, the mechanism:
A- insulin increases glucose uptake into the target cells by facilitating the insertion
of glucose transporters into cell membranes, resulting in glucose to enter the cell
and a decrease in plasma glucose concentration.
B- insulin promotes glycogenesis (formation of glycogen) from glucose in the muscle
and liver, and it inhibits glycogenolysis.
C- insulin decreases gluconeogenesis, it increases the production of fructose
2,6-biphosphate, increasing phosphofructokinase activity.
Actions of insulin
Insulin acts on liver, adipose tissue and muscle
1- insulin decreases the blood glucose concentration, the mechanism:
A- insulin increases glucose uptake into the target cells by facilitating the insertion
of glucose transporters into cell membranes, resulting in glucose to enter the cell
and a decrease in plasma glucose concentration.
B- insulin promotes glycogenesis (formation of glycogen) from glucose in the muscle
and liver, and it inhibits glycogenolysis.
C- insulin decreases gluconeogenesis, it increases the production of fructose
2,6-biphosphate, increasing phosphofructokinase activity.
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Actions of insulin, continued
Insulin acts on liver, adipose tissue and muscle
2- insulin decreases blood fatty acid and ketoacid concentrations:
A- insulin stimulates fat deposition and inhibits lipolysis in adipose tissue,
B- insulin inhibits ketoacid formation in the liver, because decreased fatty acid
degradation provides less acetyl CoA substrate for ketoacid formation.
3- insulin decreases blood K+ concentration, increases K+ uptake into cells,
which decreases blood K+ concentration.
Actions of insulin, continued
Insulin acts on liver, adipose tissue and muscle
2- insulin decreases blood fatty acid and ketoacid concentrations:
A- insulin stimulates fat deposition and inhibits lipolysis in adipose tissue,
B- insulin inhibits ketoacid formation in the liver, because decreased fatty acid
degradation provides less acetyl CoA substrate for ketoacid formation.
3- insulin decreases blood K+ concentration, increases K+ uptake into cells,
which decreases blood K+ concentration.
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Somatostatin
Regulatory effect on insulin and glucagon
Local action on islet cells to depress both insulin and glucagon
Indirect effect via decreasing GI motility (stomach, SI and GB)
Indirect effect via decreasing secretion and absorption in the GI tract
Effect – prolong digestive window for nutrient assimilation into blood and decreases nutrient utilization
Somatostatin
Regulatory effect on insulin and glucagon
Local action on islet cells to depress both insulin and glucagon
Indirect effect via decreasing GI motility (stomach, SI and GB)
Indirect effect via decreasing secretion and absorption in the GI tract
Effect – prolong digestive window for nutrient assimilation into blood and decreases nutrient utilization
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Pineal Gland
How does the retina transmit information about light-dark exposure to the pineal gland? Light exposure to the retina is first relayed to the suprachiasmatic nucleus of the hypothalamus, an area of the brain well known to coordinate biological clock signals. Fibers from the hypothalamus descend to the spinal cord and ultimately project to the superior cervical ganglia, from which post-ganglionic neurons ascend back to the pineal gland. Thus, the pineal is similar to the adrenal medulla in the sense that it transduces signals from the sympathetic nervous system into a hormonal signal.
Melatonin: Synthesis, Secretion and Receptors
The precursor to melatonin is serotonin, a neurotransmitter that itself is derived from the amino acid tryptophan. Within the pineal gland, serotonin is acetylated and then methylated to yield melatonin.
Synthesis and secretion of melatonin is dramatically affected by light exposure to the eyes.
Pineal Gland
How does the retina transmit information about light-dark exposure to the pineal gland? Light exposure to the retina is first relayed to the suprachiasmatic nucleus of the hypothalamus, an area of the brain well known to coordinate biological clock signals. Fibers from the hypothalamus descend to the spinal cord and ultimately project to the superior cervical ganglia, from which post-ganglionic neurons ascend back to the pineal gland. Thus, the pineal is similar to the adrenal medulla in the sense that it transduces signals from the sympathetic nervous system into a hormonal signal.
Melatonin: Synthesis, Secretion and Receptors
The precursor to melatonin is serotonin, a neurotransmitter that itself is derived from the amino acid tryptophan. Within the pineal gland, serotonin is acetylated and then methylated to yield melatonin.
Synthesis and secretion of melatonin is dramatically affected by light exposure to the eyes.
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Gonads and placentaEstrogenProgesteroneTestosteroneHCG
Gonads and placentaEstrogenProgesteroneTestosteroneHCG
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ProstaglandinsOne of a number of hormone-like substances that participate in a wide range of body functions such as the contraction and relaxation of smooth muscle, the dilation and constriction of blood vessels, control of blood pressure, and modulation of inflammation. Prostaglandins are derived from a chemical called arachidonic acid (is released from phospholipids in the plasma membrane and may then enter one of two possible metabolic pathway:1. The arachidonic acid is converted by the enzyme cyclooxygenase into a prostaglandin:-PGI2, antiplatelet aggregation, vasodilation-PGE2, smooth muscle relaxation, vasodilation-PGF2alpha, smooth muscle contraction, vasoconstriction-TXA2 (thromboxane A2), platelet aggregation, vasoconstriction2. Arachidonic acid is converted by the enzyme lipoxygenase into leukotrienes which are largely responsible for the symptoms of asthma.-Inflammation-Bronchoconstriction-Vasoconstriction
ProstaglandinsOne of a number of hormone-like substances that participate in a wide range of body functions such as the contraction and relaxation of smooth muscle, the dilation and constriction of blood vessels, control of blood pressure, and modulation of inflammation. Prostaglandins are derived from a chemical called arachidonic acid (is released from phospholipids in the plasma membrane and may then enter one of two possible metabolic pathway:1. The arachidonic acid is converted by the enzyme cyclooxygenase into a prostaglandin:-PGI2, antiplatelet aggregation, vasodilation-PGE2, smooth muscle relaxation, vasodilation-PGF2alpha, smooth muscle contraction, vasoconstriction-TXA2 (thromboxane A2), platelet aggregation, vasoconstriction2. Arachidonic acid is converted by the enzyme lipoxygenase into leukotrienes which are largely responsible for the symptoms of asthma.-Inflammation-Bronchoconstriction-Vasoconstriction
72
Inhibitors of Prostaglandins synthesisNonsteroidal anti-inflammatory drugs (NSAIDs)Indomethacin IbuprofenThese drugs produce their effects because they specifically inhibit the cyclooxygenase enzyme that is needed for prostaglandin synthesis.
Inhibitors of Prostaglandins synthesisNonsteroidal anti-inflammatory drugs (NSAIDs)Indomethacin IbuprofenThese drugs produce their effects because they specifically inhibit the cyclooxygenase enzyme that is needed for prostaglandin synthesis.
73
Spermatogenesis:
Spermatogenesis refers to the entire sequence of events by which primitive germ cells (spermatogonia) are transformed into sperms or spermatozoa.
This maturation process of germ cells begins at puberty (13 years) and continues into old age.
Spermatogonia, which have been dormant in the seminiferous tubules of the testes since the fetal period, begin to increase in number at puberty .After several mitotic divisions, the spermatogonia grow and transform into primary spermatocytes.
Each Primary spermatocyte subsequently undergoes a reduction division (the first meiotic division) to form two haploid secondary spermatocytes.
Secondary spermatocytes undergo a second meiotic division to form four haploid spermatids.
Spermatids are gradually transformed into four mature sperms by a differentiation process known as spermiogenesis.
Sperms are transported to the epididymis, ductus deferens, and urethra.
Sertoli cells: lining the seminiferous tubules support and nurture the germ cells, and may be involved in the regulation of spermatogenesis.
Spermatogenesis:
Spermatogenesis refers to the entire sequence of events by which primitive germ cells (spermatogonia) are transformed into sperms or spermatozoa.
This maturation process of germ cells begins at puberty (13 years) and continues into old age.
Spermatogonia, which have been dormant in the seminiferous tubules of the testes since the fetal period, begin to increase in number at puberty .After several mitotic divisions, the spermatogonia grow and transform into primary spermatocytes.
Each Primary spermatocyte subsequently undergoes a reduction division (the first meiotic division) to form two haploid secondary spermatocytes.
Secondary spermatocytes undergo a second meiotic division to form four haploid spermatids.
Spermatids are gradually transformed into four mature sperms by a differentiation process known as spermiogenesis.
Sperms are transported to the epididymis, ductus deferens, and urethra.
Sertoli cells: lining the seminiferous tubules support and nurture the germ cells, and may be involved in the regulation of spermatogenesis.
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Mature sperm
- Head of the sperm (contains nucleus)
- Acrosome (enzymes, acrosin)
- Tail of the sperm: middle piece (mitochodria, ATP), principal piece, end piece.
Mature sperm
- Head of the sperm (contains nucleus)
- Acrosome (enzymes, acrosin)
- Tail of the sperm: middle piece (mitochodria, ATP), principal piece, end piece.
75
MALE REPRODUCTIVE SYSTEM
The Hypothalamic-Pituitary-Gonadal AxisThe hypothalamus is the integrative center of the reproductive axis and receives messages from both the central nervous system and the testes to regulate the production and secretion of gonadotropin releasing hormone (GnRH).
Neurotransmitters and neuropeptides have both inhibitory and stimulatory influence on the hypothalamus. The hypothalamus releases GnRH in a pulsatile nature which appears to be essential for stimulating the production and release of both luteinizing hormone (LH) and follicle stimulating hormone (FSH).
Paradoxically, after the initial stimulation of these gonadotropins, the exposure to constant GnRH results in inhibition of their release.
LH and FSH are produced in the anterior pituitary and are secreted episodically in response to the pulsatile release of GnRH.
LH and FSH both bind to specific receptors on the Leydig cells and Sertoli cells within the testis.
MALE REPRODUCTIVE SYSTEM
The Hypothalamic-Pituitary-Gonadal AxisThe hypothalamus is the integrative center of the reproductive axis and receives messages from both the central nervous system and the testes to regulate the production and secretion of gonadotropin releasing hormone (GnRH).
Neurotransmitters and neuropeptides have both inhibitory and stimulatory influence on the hypothalamus. The hypothalamus releases GnRH in a pulsatile nature which appears to be essential for stimulating the production and release of both luteinizing hormone (LH) and follicle stimulating hormone (FSH).
Paradoxically, after the initial stimulation of these gonadotropins, the exposure to constant GnRH results in inhibition of their release.
LH and FSH are produced in the anterior pituitary and are secreted episodically in response to the pulsatile release of GnRH.
LH and FSH both bind to specific receptors on the Leydig cells and Sertoli cells within the testis.
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MALE REPRODUCTIVE SYSTEM (continued)
The Hypothalamic-Pituitary-Gonadal Axis
Testosterone, the major secretory product of the testes, is a primary inhibitor of LH secretion in males.
Testosterone may be metabolized in peripheral tissue to the potent androgen dihydrotestosterone or the potent estrogen estradiol.
These androgens and estrogens act independently to modulate LH secretion.
The mechanism of feedback control of FSH is regulated by a Sertoli cell product called inhibin.
Decreases in spermatogenesis are accompanied by decreased production of inhibin and this reduction in negative feedback is associated with reciprocal elevation of FSH levels.
Isolated increased levels of FSH constitute an important, sensitive marker of the state of the germinal epithelium.
MALE REPRODUCTIVE SYSTEM (continued)
The Hypothalamic-Pituitary-Gonadal Axis
Testosterone, the major secretory product of the testes, is a primary inhibitor of LH secretion in males.
Testosterone may be metabolized in peripheral tissue to the potent androgen dihydrotestosterone or the potent estrogen estradiol.
These androgens and estrogens act independently to modulate LH secretion.
The mechanism of feedback control of FSH is regulated by a Sertoli cell product called inhibin.
Decreases in spermatogenesis are accompanied by decreased production of inhibin and this reduction in negative feedback is associated with reciprocal elevation of FSH levels.
Isolated increased levels of FSH constitute an important, sensitive marker of the state of the germinal epithelium.
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Male fertility
Depends on the number and motility of sperm.
1. The average volume of semen in a normal, fertile male ejaculate is 3.5 ml, with a concentration of about 100 million sperm/ml of semen.
2. Normally up to 10% of sperm in an ejaculate may be grossly deformed (two heads or two tails), but these sperms probably do not fertilize an oocyte owing to their lack of motility.
Male fertility
Depends on the number and motility of sperm.
1. The average volume of semen in a normal, fertile male ejaculate is 3.5 ml, with a concentration of about 100 million sperm/ml of semen.
2. Normally up to 10% of sperm in an ejaculate may be grossly deformed (two heads or two tails), but these sperms probably do not fertilize an oocyte owing to their lack of motility.
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Male organs:
Testes
Epididymis
Vas deferens
The urethraThe prostate
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Male organs:
Testes
Epididymis
Vas deferens
The urethraThe prostate
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Erection, Emission, and Ejaculation
Erection is as a result of blood flow into the erectile tissues of the penis.
Erection is achieved by parasympathetic nerve-induced vasodilation of arterioles that allows blood to flow into the corpora cavernosa of the penis.
The neurotransmitter that mediates this increased blood flow is nitric oxide. Nitric oxide, released in the penis in response to parasympathetic nerve stimulation, diffuses into the smooth muscle cells of blood vesseles and stimulates the production of cGMP. The cGMP, in turn, causes the vascular smooth muscle to relax, so that blood can flow into the corpora cavernosa.
Emission is controlled by sympathetic.
Ejuaculation is controlled by sympathetic and parasympathetic.
Erection, Emission, and Ejaculation
Erection is as a result of blood flow into the erectile tissues of the penis.
Erection is achieved by parasympathetic nerve-induced vasodilation of arterioles that allows blood to flow into the corpora cavernosa of the penis.
The neurotransmitter that mediates this increased blood flow is nitric oxide. Nitric oxide, released in the penis in response to parasympathetic nerve stimulation, diffuses into the smooth muscle cells of blood vesseles and stimulates the production of cGMP. The cGMP, in turn, causes the vascular smooth muscle to relax, so that blood can flow into the corpora cavernosa.
Emission is controlled by sympathetic.
Ejuaculation is controlled by sympathetic and parasympathetic.
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The Testes
Leydig CellsLeydig cells secrete Testosterone episodically in response to LH pulses which has a diurnal pattern, with the peak level in the early morning and the trough level in the late afternoon or early evening. In the intact testis, LH receptors decrease or down-regulate after exogenous LH administration.
Seminiferous TubulesThe seminiferous tubules contain all the germ cells at various stages of maturation and their supporting Sertoli cells. These account for 85-90% of the testicular volume. Sertoli cells are a fixed-population of non-dividing support cells.
The Testes
Leydig CellsLeydig cells secrete Testosterone episodically in response to LH pulses which has a diurnal pattern, with the peak level in the early morning and the trough level in the late afternoon or early evening. In the intact testis, LH receptors decrease or down-regulate after exogenous LH administration.
Seminiferous TubulesThe seminiferous tubules contain all the germ cells at various stages of maturation and their supporting Sertoli cells. These account for 85-90% of the testicular volume. Sertoli cells are a fixed-population of non-dividing support cells.
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Oogenesis
Refers to the transformation of oogonia into mature oocytes.
Prenatal maturation of oocytes:
During early fetal life, oogonia proliferate by mitotic division. Oogonia enlarge to form primary oocytes before birth.
As a primary oocyte forms, connective tissue cells surround this single layer, follicular epithelial cells.
It leads to formation of a primordial follicle.
As the primary oocyte enlarges during puberty, the follicular epithelial cells become cuboidal in shape and then forming a primary follicle.
Primary oocyte becomes surrounded by a covering of amorphous acellular glycoprotein material called the zona pellucida.
When the primary follicle has more than one layer of cuboidal follicular cells, it is called a maturing or secondary follicle.
Primary oocyte begin the first meiotic division before birth, and remain in suspended until sexual maturity and the reproductive cycles begin during puberty.
The follicular cells surrounding the primary oocyte secrete oocyte maturation inhibitor (OMI), which keeps the meiotic process of the oocyte arrested.
Oogenesis
Refers to the transformation of oogonia into mature oocytes.
Prenatal maturation of oocytes:
During early fetal life, oogonia proliferate by mitotic division. Oogonia enlarge to form primary oocytes before birth.
As a primary oocyte forms, connective tissue cells surround this single layer, follicular epithelial cells.
It leads to formation of a primordial follicle.
As the primary oocyte enlarges during puberty, the follicular epithelial cells become cuboidal in shape and then forming a primary follicle.
Primary oocyte becomes surrounded by a covering of amorphous acellular glycoprotein material called the zona pellucida.
When the primary follicle has more than one layer of cuboidal follicular cells, it is called a maturing or secondary follicle.
Primary oocyte begin the first meiotic division before birth, and remain in suspended until sexual maturity and the reproductive cycles begin during puberty.
The follicular cells surrounding the primary oocyte secrete oocyte maturation inhibitor (OMI), which keeps the meiotic process of the oocyte arrested.
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Oogenesis (continued):
2. Postnatal maturation of oocytes:
Begins during puberty, usually one follicle matures each month and ovulation occurs.
No primary oocytes form after birth in females, the primary remain dormant in the ovarian follicles until puberty.
As a follicle matures, the primary oocyte increases in size and shortly before ovulation, completes the first meiotic division.
At ovulation the nucleus of the secondary oocyte begins the second meiotic division.
If a sperm penetrates the secondary oocyte, the second meiotic division is completed, (the fertilized oocyte, or mature ovum.)
maturation of the oocyte is complete.
Oogenesis (continued):
2. Postnatal maturation of oocytes:
Begins during puberty, usually one follicle matures each month and ovulation occurs.
No primary oocytes form after birth in females, the primary remain dormant in the ovarian follicles until puberty.
As a follicle matures, the primary oocyte increases in size and shortly before ovulation, completes the first meiotic division.
At ovulation the nucleus of the secondary oocyte begins the second meiotic division.
If a sperm penetrates the secondary oocyte, the second meiotic division is completed, (the fertilized oocyte, or mature ovum.)
maturation of the oocyte is complete.
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Structure of the female reproductive organs
Uterus
The uterus averages 7 to 8 cm in length, 5-7 cm in width at its superior part, and 2-3 cm in thickness. It consists:
Body
Cervix
Cervical canal (internal os , external os)
The wall: Perimetrium
Myometrium
Endometrium
Uterine tubes
- Infundibulum
- Ampulla
- Isthmus
- Uterine part
Ovaries
The ovary is almond-shaped.
Structure of the female reproductive organs
Uterus
The uterus averages 7 to 8 cm in length, 5-7 cm in width at its superior part, and 2-3 cm in thickness. It consists:
Body
Cervix
Cervical canal (internal os , external os)
The wall: Perimetrium
Myometrium
Endometrium
Uterine tubes
- Infundibulum
- Ampulla
- Isthmus
- Uterine part
Ovaries
The ovary is almond-shaped.
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Pseudohermaphroditism or psuedo-hermaphroditism,
Klinefelter syndrome (XXY)
Pseudohermaphroditism or psuedo-hermaphroditism,
Klinefelter syndrome (XXY)
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Ovulation
Ovulation is triggered by a surge of LH production. Ovulation usually follows the LH peak by 12-24 hours.
A small avascular spot, the stigma, soon appears on this swelling, then the stigma ruptures, expelling the secondary oocyte with the follicular fluid.
The expelled secondary oocyte is surrounded by the zona pellucida and follicular cells, corona radiata.
Corpus luteum
It secrets progesterone and estrogen.
If the oocyte is fertilized, the corpus luteum enlarges to form a corpus luteum of pregnancy and increases its hormone production. (under control human chorionic gonadotropin, hCG).
If the oocyte is not fertilized corpus luteum
begins to degenerate about 10 to 12 days
after ovulation. It is transformed into white
scar tissue in the ovary called a corpus albicans.
Ovulation
Ovulation is triggered by a surge of LH production. Ovulation usually follows the LH peak by 12-24 hours.
A small avascular spot, the stigma, soon appears on this swelling, then the stigma ruptures, expelling the secondary oocyte with the follicular fluid.
The expelled secondary oocyte is surrounded by the zona pellucida and follicular cells, corona radiata.
Corpus luteum
It secrets progesterone and estrogen.
If the oocyte is fertilized, the corpus luteum enlarges to form a corpus luteum of pregnancy and increases its hormone production. (under control human chorionic gonadotropin, hCG).
If the oocyte is not fertilized corpus luteum
begins to degenerate about 10 to 12 days
after ovulation. It is transformed into white
scar tissue in the ovary called a corpus albicans.
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Corpus Albicans :
If fertilization does not occur, the corpus luteum degenerates and is replaced by connective tissue forming a corpus albicans.
Corpus Albicans :
If fertilization does not occur, the corpus luteum degenerates and is replaced by connective tissue forming a corpus albicans.
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FERTILIZATION
Fertilization normally takes place within the uterine tubes (ampulla), after ovulation has occurred. During the menstrual mid cycle, the cervical mucus changes to become more abundant, thinner and more watery. These changes serve to facilitate entry of the sperm into the uterus and to protect the sperm from the highly acidic vaginal secretions.
Passage of sperm through corona radiata surrounding the zona pellucida of an oocyte.
Penetration of zona pellucida surrounding the oocyte. (enzymes: neuraminidase, acrosin)
Fusion of plasma membranes of the oocyte and sperm
Completion of second meiotic division of oocyte and formation of female pronucleus
Formation of male pronucleus
Membranes of pronuclei break down, the chromosomes condense and become arranged for a mitotic cell division.
The fertilized oocyte or zygote is a unicellular embryo. The combination of 23 chromosomes in each pronucleus results in a zygote with 46 chromosomes.
FERTILIZATION
Fertilization normally takes place within the uterine tubes (ampulla), after ovulation has occurred. During the menstrual mid cycle, the cervical mucus changes to become more abundant, thinner and more watery. These changes serve to facilitate entry of the sperm into the uterus and to protect the sperm from the highly acidic vaginal secretions.
Passage of sperm through corona radiata surrounding the zona pellucida of an oocyte.
Penetration of zona pellucida surrounding the oocyte. (enzymes: neuraminidase, acrosin)
Fusion of plasma membranes of the oocyte and sperm
Completion of second meiotic division of oocyte and formation of female pronucleus
Formation of male pronucleus
Membranes of pronuclei break down, the chromosomes condense and become arranged for a mitotic cell division.
The fertilized oocyte or zygote is a unicellular embryo. The combination of 23 chromosomes in each pronucleus results in a zygote with 46 chromosomes.
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Menstrual Cycle-Follicular Phase-Luteal Phase-Secretory Phase
Menstrual Cycle-Follicular Phase-Luteal Phase-Secretory Phase
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Pregnancy
Before pregnancy begins, a female oocyte must join with a sperm in a process referred to in medicine as "fertilization", or commonly known as "conception". Fertilization usually occurs through the act of sexual intercourse, in which a sperm penetrates and fertilizes an egg.
Traditionally a human pregnancy is considered to last approximately 40 weeks (280 days) from the LMP, or 38 weeks (266 days) from the date of fertilization.
- Presence of human chorionic gonadotropin (hCG) in the blood and urine, detectable by laboratory testing; this is the most reliable early sign of pregnancy
- Missed menstrual period.
In the post-implantation phase, the blastocyst secretes a hormone named human chorionic gonadotropin which in turn, stimulates the corpus luteum in the woman's ovary to continue producing progesterone. This acts to maintain the lining of the uterus so that the embryo will continue to be nourished.
Pregnancy
Before pregnancy begins, a female oocyte must join with a sperm in a process referred to in medicine as "fertilization", or commonly known as "conception". Fertilization usually occurs through the act of sexual intercourse, in which a sperm penetrates and fertilizes an egg.
Traditionally a human pregnancy is considered to last approximately 40 weeks (280 days) from the LMP, or 38 weeks (266 days) from the date of fertilization.
- Presence of human chorionic gonadotropin (hCG) in the blood and urine, detectable by laboratory testing; this is the most reliable early sign of pregnancy
- Missed menstrual period.
In the post-implantation phase, the blastocyst secretes a hormone named human chorionic gonadotropin which in turn, stimulates the corpus luteum in the woman's ovary to continue producing progesterone. This acts to maintain the lining of the uterus so that the embryo will continue to be nourished.
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Labor and Parturition
Uterine contractions are known to be stimulated by two agents:
Oxytocin
2. prostaglandins (PGF2alpha, PGE2)
Labor and Parturition
Uterine contractions are known to be stimulated by two agents:
Oxytocin
2. prostaglandins (PGF2alpha, PGE2)
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Defense mechanisms-Innate immunity (nonspecific)Adaptive immunity (specific)
Defense mechanisms-Innate immunity (nonspecific)Adaptive immunity (specific)
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Innate immunity
Innate immunity includes both external and internal defenses. These defenses are always present in the body and represent the first line of defense against invasion by potential pathogens.
Innate immunity
Innate immunity includes both external and internal defenses. These defenses are always present in the body and represent the first line of defense against invasion by potential pathogens.
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Innate immunity
Phagocytosisare three major groups of phagocytic cells:1. neutrophils2. the cells of the mononuclear phagocyte system, including monocytes in the blood and macrophages derived from monocytes in the connective tissues3. organ-specific phagocytes in the liver, spleen (Kupffer cells) , lymph nodes, lungs, brain ( microglia).These phagocytes remove foreign particles from the blood, so that blood is usually sterile after a a few passes through the liver and spleen.Connective tissues have a resident population of all leukocyte type. Leukocytes act to the site of an infection by chemotaxis.
Innate immunity
Phagocytosisare three major groups of phagocytic cells:1. neutrophils2. the cells of the mononuclear phagocyte system, including monocytes in the blood and macrophages derived from monocytes in the connective tissues3. organ-specific phagocytes in the liver, spleen (Kupffer cells) , lymph nodes, lungs, brain ( microglia).These phagocytes remove foreign particles from the blood, so that blood is usually sterile after a a few passes through the liver and spleen.Connective tissues have a resident population of all leukocyte type. Leukocytes act to the site of an infection by chemotaxis.
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Innate immunity
Chemotaxis: movement toward chemical attractants which are a subclass of cytokines known as chemokines. Neutrophils are the first to arrive at the site of an infection; monocytes arrive later and can be transformed into macrophages.
Innate immunity
Chemotaxis: movement toward chemical attractants which are a subclass of cytokines known as chemokines. Neutrophils are the first to arrive at the site of an infection; monocytes arrive later and can be transformed into macrophages.
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Innate immunity
FEVERTemperature is regulated in the hypothalamus, in response to PGE2. PGE2 release, in turn, comes from a trigger, a pyrogen. The hypothalamus generates a response back to the rest of the body, making it increase the temperature set-point.
Innate immunity
FEVERTemperature is regulated in the hypothalamus, in response to PGE2. PGE2 release, in turn, comes from a trigger, a pyrogen. The hypothalamus generates a response back to the rest of the body, making it increase the temperature set-point.
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Innate immunity
PyrogensA pyrogen is a substance that induces fever. These can be either internal (endogenous) or external (exogenous). The bacterial substance lipopolysaccharide (LPS) is an example of an exogenous pyrogen.
Innate immunity
PyrogensA pyrogen is a substance that induces fever. These can be either internal (endogenous) or external (exogenous). The bacterial substance lipopolysaccharide (LPS) is an example of an exogenous pyrogen.
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Innate immunity
EndogenousThe cytokines (such as interleukin 1) are a part of the innate immune system, produced by phagocytic cells, and cause the increase in the thermoregulatory set-point in the hypothalamus. Other examples of endogenous pyrogens are interleukin 6 (IL-6), and the tumor necrosis factor-alpha.These cytokine factors are released into general circulation where they migrate to the circumventricular organs of the brain, where the blood-brain barrier is reduced. The cytokine factors bind with endothelial receptors on vessel walls, or interact with local microglial cells. When these cytokine factors bind, they activate the arachidonic acid pathway.
Innate immunity
EndogenousThe cytokines (such as interleukin 1) are a part of the innate immune system, produced by phagocytic cells, and cause the increase in the thermoregulatory set-point in the hypothalamus. Other examples of endogenous pyrogens are interleukin 6 (IL-6), and the tumor necrosis factor-alpha.These cytokine factors are released into general circulation where they migrate to the circumventricular organs of the brain, where the blood-brain barrier is reduced. The cytokine factors bind with endothelial receptors on vessel walls, or interact with local microglial cells. When these cytokine factors bind, they activate the arachidonic acid pathway.
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PGE2 release
PGE2 release comes from the arachidonic acid pathway. This pathway (as it relates to fever), is mediated by the enzymes phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), and prostaglandin E2 synthase.
These enzymes ultimately mediate the synthesis and release of PGE2.
PGE2 is the ultimate mediator of the febrile response.
PGE2 release
PGE2 release comes from the arachidonic acid pathway. This pathway (as it relates to fever), is mediated by the enzymes phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), and prostaglandin E2 synthase.
These enzymes ultimately mediate the synthesis and release of PGE2.
PGE2 is the ultimate mediator of the febrile response.
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Adaptive immunity (specific)AntigenAn antigen or immunogen is a molecule that stimulates an immune response. Antigens are usually proteins or polysaccharides. This includes parts (coats, capsules, cell walls, flagella, fimbrae, and toxins) of bacteria, viruses, and other microorganisms. Lipids and nucleic acids are antigenic only when combined with proteins and polysaccharides. Antigen stimulate the production of specific antibodies.
Adaptive immunity (specific)AntigenAn antigen or immunogen is a molecule that stimulates an immune response. Antigens are usually proteins or polysaccharides. This includes parts (coats, capsules, cell walls, flagella, fimbrae, and toxins) of bacteria, viruses, and other microorganisms. Lipids and nucleic acids are antigenic only when combined with proteins and polysaccharides. Antigen stimulate the production of specific antibodies.
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haptensHaptens are low-molecular weight molecules which contain an antigenic determinant but which are not itself antigenic unless complexes with an immunogenic carrier.If they bind to protein and thus become antigenic determinant on the proteins.
haptensHaptens are low-molecular weight molecules which contain an antigenic determinant but which are not itself antigenic unless complexes with an immunogenic carrier.If they bind to protein and thus become antigenic determinant on the proteins.
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LymphocytesTypes of lymphocytes A stained lymphocyte surrounded by red blood cells viewed using a light microscope.The three major types of lymphocyte are: T cells, B cells and natural killer (Nk) cellsNK cells are a part of innate immune system and play a major role in defending the host from both tumors and virally infected cells. NK cells are activated in response to a family of cytokines called interferons. Activated NK cells release cytotoxic (cell-killing) granules which then destroy the altered cells.
LymphocytesTypes of lymphocytes A stained lymphocyte surrounded by red blood cells viewed using a light microscope.The three major types of lymphocyte are: T cells, B cells and natural killer (Nk) cellsNK cells are a part of innate immune system and play a major role in defending the host from both tumors and virally infected cells. NK cells are activated in response to a family of cytokines called interferons. Activated NK cells release cytotoxic (cell-killing) granules which then destroy the altered cells.
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Local inflammationInflammation is the response of the organism to the pathogen.
Local inflammationInflammation is the response of the organism to the pathogen.
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Functions of B lymphocytesB lymphocytes secrete antibodies that can bind to antigens in a specific fashion.AntibodiesAntibody proteins are also known as immunoglobulins. They are found in the gamma globulin class of plasma proteins. The five distinct bands of proteins that appear are albumin, alpha-1 globulin, alpha-2 globulin, beta globulin, and gamma globulin.These are identified by a technique called electrophoresis.There are five immunoglobulin subclasses:IgG, IgA, IgM, IgD, and IgE. Most of the antibodies in serum are in the IgG subclass, whereas most of the antibodies in external secretions (saliva and milk) are IgA, antibodies in the IgE subclass are involved in certain allergic reactions.
Functions of B lymphocytesB lymphocytes secrete antibodies that can bind to antigens in a specific fashion.AntibodiesAntibody proteins are also known as immunoglobulins. They are found in the gamma globulin class of plasma proteins. The five distinct bands of proteins that appear are albumin, alpha-1 globulin, alpha-2 globulin, beta globulin, and gamma globulin.These are identified by a technique called electrophoresis.There are five immunoglobulin subclasses:IgG, IgA, IgM, IgD, and IgE. Most of the antibodies in serum are in the IgG subclass, whereas most of the antibodies in external secretions (saliva and milk) are IgA, antibodies in the IgE subclass are involved in certain allergic reactions.
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Antibody structureAntibodies are composed of four polypeptide chains:Two are heavy (H) and two are light (L).
Antibody structureAntibodies are composed of four polypeptide chains:Two are heavy (H) and two are light (L).
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The complement systemThe combination of antibodies with antigens does not itself cause destruction of the antigens or the pathogenic organisms that contain these antigens. Antibodies serve to identify the targets for immunological attack and to activate nonspecific immune processes that destroy the invader. Bacteria that are buttered with antibodies, for example, are better targets for phagocytosis by neutrophils and macrophages. The ability of antibodies to stimulate phagocytsis is termed opsonization. Immune destruction of bacteria is also promoted by antibody-induced activation of a system of serum proteins known as complement.
The complement systemThe combination of antibodies with antigens does not itself cause destruction of the antigens or the pathogenic organisms that contain these antigens. Antibodies serve to identify the targets for immunological attack and to activate nonspecific immune processes that destroy the invader. Bacteria that are buttered with antibodies, for example, are better targets for phagocytosis by neutrophils and macrophages. The ability of antibodies to stimulate phagocytsis is termed opsonization. Immune destruction of bacteria is also promoted by antibody-induced activation of a system of serum proteins known as complement.
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The complement proteins are designated C1 through C9. These proteins are present in an inactive state within plasma and other body fluids and become activated by the attachment of antibodies to antigens. In terms of their functions, the complement proteins can be subdivided into three components:1. recognition-C12. activation-C4, C2, and C3 in that order3. attack-C5 through C9
The complement proteins are designated C1 through C9. These proteins are present in an inactive state within plasma and other body fluids and become activated by the attachment of antibodies to antigens. In terms of their functions, the complement proteins can be subdivided into three components:1. recognition-C12. activation-C4, C2, and C3 in that order3. attack-C5 through C9
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The attack phase consists of complement fixation, in which complement proteins attach to the cell membrane and destroy the victim cell.In the classic pathway. IgG, IgM antibodies activate C1, which catalyzes the hydrolysis of C4 into two fragments, C4a and C4b. The C4b fragment binds to the cell membrane and becomes an active enzyme. Then, through an intermediate step involving the splitting of C2, C3 is cleaved into C3a and C3b. The C3b converts C5 into C5a and C5b. The C3a and C5a stimulate mast cells to release histamine; C5a additionally serves as a chemokine to attract neutrophils and monocytes to the site of infection. Meanwhile, C5 through C9 are inserted into the bacterial cell membrane to form a membrane attack complex. The attack complex is a large pore that can kill the bacterial cell through the osmotic influx of water. Note that the complement proteins, not the antibodies directly, kill the cell; antibodies serve only as activators of this process in the classic pathway.
The attack phase consists of complement fixation, in which complement proteins attach to the cell membrane and destroy the victim cell.In the classic pathway. IgG, IgM antibodies activate C1, which catalyzes the hydrolysis of C4 into two fragments, C4a and C4b. The C4b fragment binds to the cell membrane and becomes an active enzyme. Then, through an intermediate step involving the splitting of C2, C3 is cleaved into C3a and C3b. The C3b converts C5 into C5a and C5b. The C3a and C5a stimulate mast cells to release histamine; C5a additionally serves as a chemokine to attract neutrophils and monocytes to the site of infection. Meanwhile, C5 through C9 are inserted into the bacterial cell membrane to form a membrane attack complex. The attack complex is a large pore that can kill the bacterial cell through the osmotic influx of water. Note that the complement proteins, not the antibodies directly, kill the cell; antibodies serve only as activators of this process in the classic pathway.
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Functions of T lymphocytes
T cell subsetsMolecular association of CD8+ T cells with MHC class I and CD4+ T cells with MHC class IISeveral different subsets of T cells have been described, each with a distinct function.
Functions of T lymphocytes
T cell subsetsMolecular association of CD8+ T cells with MHC class I and CD4+ T cells with MHC class IISeveral different subsets of T cells have been described, each with a distinct function.
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Functions of T lymphocytes
Helper T cells are the "middlemen" of the adaptive immune system. Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or "help" the immune response. Depending on the cytokine signals received, these cells differentiate into Th1, Th2, Th17 or other subsets, which secrete different cytokines.
Functions of T lymphocytes
Helper T cells are the "middlemen" of the adaptive immune system. Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or "help" the immune response. Depending on the cytokine signals received, these cells differentiate into Th1, Th2, Th17 or other subsets, which secrete different cytokines.
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Functions of T lymphocytes
Cytotoxic T cells (Tc cells) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8+ T cells, since they express the CD8 glycoprotein at their surface. Through interaction with helper T cells, these cells can be transformed into suppressor T cells which prevent autoimmune diseases such as experimental autoimmune encephalomyelitis.(MHC 1)
Functions of T lymphocytes
Cytotoxic T cells (Tc cells) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8+ T cells, since they express the CD8 glycoprotein at their surface. Through interaction with helper T cells, these cells can be transformed into suppressor T cells which prevent autoimmune diseases such as experimental autoimmune encephalomyelitis.(MHC 1)
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Functions of T lymphocytes
Memory T cells are a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen, thus providing the immune system with "memory" against past infections. Memory T cells comprise two subtypes: central memory T cells (TCM cells) and effector memory T cells (TEM cells). Memory cells may be either CD4+ or CD8+.
Functions of T lymphocytes
Memory T cells are a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen, thus providing the immune system with "memory" against past infections. Memory T cells comprise two subtypes: central memory T cells (TCM cells) and effector memory T cells (TEM cells). Memory cells may be either CD4+ or CD8+.
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Functions of T lymphocytes
Regulatory T cells (Treg cells), formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell mediated immunity towards the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Two major classes of CD4+ regulatory T cells have been described, including: *The naturally occurring Treg cells and the adaptive Treg cells. Naturally occurring Treg cells (also known as CD4+CD25+FoxP3+ Treg cells) arise in the thymus, *The adaptive Treg cells (also known as Tr1 cells or Th3 cells) may originate during a normal immune response.
Functions of T lymphocytes
Regulatory T cells (Treg cells), formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell mediated immunity towards the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Two major classes of CD4+ regulatory T cells have been described, including: *The naturally occurring Treg cells and the adaptive Treg cells. Naturally occurring Treg cells (also known as CD4+CD25+FoxP3+ Treg cells) arise in the thymus, *The adaptive Treg cells (also known as Tr1 cells or Th3 cells) may originate during a normal immune response.
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Natural Killer T cells (NKT cells) are a special kind of lymphocyte that bridges the adaptive immune system with the innate immune system. Unlike conventional T cells that recognize peptide antigen presented by major histocompatibility complex (MHC) molecules, NKT cells recognize glycolipid antigen presented by a molecule called CD1d.
Natural Killer T cells (NKT cells) are a special kind of lymphocyte that bridges the adaptive immune system with the innate immune system. Unlike conventional T cells that recognize peptide antigen presented by major histocompatibility complex (MHC) molecules, NKT cells recognize glycolipid antigen presented by a molecule called CD1d.
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Diseases caused by the immune system1. Autoimmunity (example: Diabetes type I)Autoimmunity is the failure of an organism to recognize its own constituent parts (down to the sub-molecular levels) as "self", which results in an immune response against its own cells and tissues. 2. Complex diseases3. Allergya. Immediate hypersensitivityb. Delayed hypersensitivity
Diseases caused by the immune system1. Autoimmunity (example: Diabetes type I)Autoimmunity is the failure of an organism to recognize its own constituent parts (down to the sub-molecular levels) as "self", which results in an immune response against its own cells and tissues. 2. Complex diseases3. Allergya. Immediate hypersensitivityb. Delayed hypersensitivity
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Allergya. Immediate hypersensitivityresults when an allergen provokes the production of antibodies in the IgE class. These antibodies attach to tissue mast cells and stimulate the release of chemicals from the mast cells.b. Delayed hypersensitivityas in contact dermatitis, is a cell-mediated response of T lymphocytes.
Allergya. Immediate hypersensitivityresults when an allergen provokes the production of antibodies in the IgE class. These antibodies attach to tissue mast cells and stimulate the release of chemicals from the mast cells.b. Delayed hypersensitivityas in contact dermatitis, is a cell-mediated response of T lymphocytes.
