Slide set 3 Flashcards
Two basic types of physiological signals
Electrical signals (changes in membrane potential) Chemical signals (molecules in extracellular fluid)
4 basic methods of cell-to-cell communication
Gap junctions
Contract-dependent signals
Chemical that diffuse through the extracellular fluid to act on cells close by
Long-distance communication
Explain gap junctions
Allow direct cytoplasmic transfer of electrical and chemical signals between adjacent cells
When open, ions, amino acids, ATP, cAMP diffuse directly
from the cytoplasm of one cell to the cytoplasm of the next
- Larger molecules cannot pass through
- The only means by which electrical signals can pass directly
from cell to cell
Explain contact-dependent signals
When surface molecules on one cell membrane bind to surface molecules on another
Occurs in immune system and during growth
and development
Long-distance cell communication uses
A combination of chemical signals transported by the blood
Connexins are used ___
They form a union for gap junctions
What type of signaling includes cell-adhesion molecules
Contact-dependent signals
Also integrins are involved
Methods of chemical communication
Autocrine signals act on the same cell that secreted
them. Paracrine signals are secreted by one cell and
diffuse to adjacent cells
Characterize long distance communication
Hormones are secreted by endocrine
glands or cells into the blood. Only target
cells with receptors for the hormone will
respond to the signal.
Neurotransmitters are chemicals secreted
by neurons that diffuse across a small gap
to the target cell. Neurons use electrical
signals as well.
Neurotransmitters have ___ effect
rapid
What are neurohormones
Chemicals released by neurons onto the blood for action at distant targets
Cytokines may act as both
Local and long-distance signals
Where cytokines are synthesized, what are their roles, and how they are made
- Are synthesized and secreted by all nucleated
cells (not produced by specialized cells) - Control cell development, differentiation, and
immune responses - Act on a broader spectrum of target cells than
hormones - Made on demand (not stored)
Features shared by all signal pathways
- The signal molecule (ligand/first messenger)brings information to the
target cell - Ligand-receptor binding activates the receptor
- The receptor activates one or more intracellular signal molecules
- The last signal molecule initiates synthesis of target proteins or modifies
existing target proteins to create a response
Slide
The location of ligand/receptor binding is largely dependent
on whether a signal molecule is __________or ___________
Hydrophobic
Hydrophylic
________ signal molecules can diffuse through the
phospholipid bilayer binding to ___________ or __________
receptors
Hydrophobic
Nuclear
Cytoplasmic
Signaling through hydrophobic molecules is relatively ___
Slow process
Lipophobic molecules ___ diffuse through the plasma membrane, they bind to ___, this process is very ___
Cannot
Extracellular receptors
Rapid
Lipophylic signal can bound to
Receptor in cytoplasmic membrane
Receptor in cytosol
Receptor in nucleus
What is the scheme of signal transduction
Signal molecule->receptor->intracellular signal->target proteins->response
What is the role of second messenger
1. Alter the gating of ion channels 2. Increase intracellular calcium (which bind to proteins to change their function) 3. Change enzyme activity, especially of protein kinases and protein phosphatases
Steps of signal transduction pathway form a ___
Cascade
WHat is the role of tyrosine kinase
Transfers a phosphate group from ATP to a tyrosine of a protein
Tyrosine kinase is an example of
Receptor-enzyme (insulin receptor)
WHat was the new discovery about insulin
That when it binds to the receptor, it causes it to translocates to the nucleus and regulates genes linked to insulin functions
Most signal transduction uses ___ proteins
G
Describe the structure of G proteins
a large and
complex family of membrane-spanning proteins
that cross the phospholipid bilayer 7 times
• Cytoplasmic tail linked to G protein, a three-part
transducer molecule
GPCR bind ___
Nucleotide guanosine
What do G proteins do when activated
Open ion channels in the membrane
– Alter enzyme activity on the cytoplasmic side of the
membrane
Explain G-protein-coupled adenylyl-cAMP system
-Signal molecule binds to G protein-linked receptor, which activates the G protein
G protein turns on adenylyl cyclase, an amplifier enzyme
Adenylyl cyclase converts ATP to cAMP
cAMP activates protein kinase A->phosphorylation of other proteins
Through GPCR we get
Amplification
Apart from cAMP GPCR there is
Phospholipase C
Four categories of membrane receptors
Receptor-channel
GPCR
Receptor-enzyme
Integrin
What is the principle of action in receptor-channel pathway
Change in membrane permeability to Na,K, Cl
It creates an electrical signal, which acts on Voltage-sensitive protein
Signal transduction through receptor-channels initiates ____
The most rapid response
How Ca concentration in cytosol can increase
It can enter from the extracellular fluid
It can be released from inner cell stores
What is Ca action inside the cell
It binds to calmodulin and then alters protein activity
Or other Ca binding proteins initiating exocytosis and movement
Agonist vs Antagonist
Agonist- also activated the receptor, because it has a similar shape
Antagonist-blocks receptor activity
What is the function of neuroendocrine system
Communicatiom,integration and control
Some neurons release ___, instead of ____
Neurohormones
Neurotransmitter
Difference between nervous and endocrine system
Effects of neurotransmitters are rapid and short lived
• Effects of hormones are slow and longer lasting
• Hormones diffuse in the blood and can therefore access
most tissues and cells
• Neurons can stimulate only muscles and glands across a
synapse.
Hormones act on their target cells in 3 basic ways
(1) by controlling the rates of enzymatic reactions,
(2) by controlling the transport of ions or molecules
across cell membranes, or
(3) by controlling gene expression and
the synthesis of proteins
What is pheromones
specialized ectohormones
that act on other organisms of the same species to elicit
a physiological or behavioral response.
Difference between neural communication specificity and endocrine system
Specificity of neural communication depends on anatomical
relationship between nerve cell and target cells.
• Unlike the endocrine system specificity is not totally reliant on
the message and cell having the correct receptor
• Which muscle moves depends on which neuron releases of
Ach as all motor neurons have Ach receptors.
Endocrine glands secrete ___. exocrine glands secrete ___
Exocrine-products
Endocrine-hormones
What glands are made out of neurosecretory tissue
Adrenal medulla
What is a master gland
Hypothalamus
Function of hypothalamus
Controls release of
anterior pituitary hormones through releasing and inhibiting factors
6 hormones secreted by an anterior pituitary gland
- Thyroid stimulating hormone
- ACTH-adrenocorticotropic hormone
- GH-Growth hormone
- FSH-Follicle-stimulating hormone and LH-luteinizing hormone
- PRL-Prolactin
- MSH-melanocyte stimulating hormone
Role of TSH
stimulates thyroid cells to produce thyroxine (T4)
and triiodothyronine (T3), brain development, metabolism, reproduction
promotes and maintains
growth and development of thyroid
Role of ACTH
stimulates cortisol secretion from adrenal
cortex
promotes and maintains normal growth
and development of cortex of adrenal gland; also stimulates
adrenal cortex to secrete some of its hormones cortisol and
aldosterone
Role of GH
Growth and metabolic effects
Role of FSH and LH
act on gonads,
growth of follicles, ovulation, Leydig cell stimulation of testosterone, FSH in male, androgen
binding protein expression by Sertoli cells
in females acts on
ovary where it stimulates primary graffian follicles to grow
toward maturity; also secretion of estrogens
- in males, FSH stimulates development of seminiferous
tubules of testes and maintains spermatogenesis. Acts on
Sertoli cells
Luteinizing hormone (LH) —in females: stimulates
formation and activity of corpus luteum of ovary; corpus
luteum secretes progesterone and estrogens when
stimulated by LH; LH also supports FSH in stimulating
maturation of follicles; in males: LH stimulates interstitial
cells (leydig cells) in testes to develop and secrete
testosterone;
Prolactin action
milk synthesis from mammary glands
During pregnancy, PRL promotes development
of the breasts, anticipating milk secretion; after
the baby is born, PRL stimulates the mother’s
mammary glands to produce milk
2 hormones of Posterior pituitary
- Vasopressin
2. Oxytocin
Action of vasopressin
Antidiuretic hormone-acts on kidneys
Oxytocin action
Milk let down
Uterine contraction
Function of pineal gland and its hormone
produces Melatonin –controls biological (circadian) rhythm
Thyroid gland: hormones and action
produces T3 and T4, calcitonin to decrease plasma controls
how quickly the body burns energy, makes proteins-metabolism regulator
Adrenal cortex produces
mineralocorticoids ex. aldosterone, corticosteroids,cortisol,androgens
Action of cortisol
increases BP and blood sugar and reduces immune responses,
anti-inflammatory)
Action of aldosterone
acts on kidney to
cause conservation of sodium, overall retention of water
Examples of androgens and action
Dehydroepiandrosterone (DHEA)
Adrenal medulla produces
epinephrine and norepinephrine (stress adaptation)
Pancreas produces
Insulin, glucagon and somatostatin
Hormones of testes and ovaries
Testes-testosteron
Ovaries- estrogen and progesterone
What is the result of hypo and hyperthyroidism
Hypo-goiter
Hyper-grave;s disease or basedov’s
How many babies are born with mental impairment and why
Iodine deficiency during pregnancy is causing almost 18 million babies a year to be
born with mental impairment
What happens in children with iodine deficiency
physical growth and development
problems, and brain development can also be severely impaired, in the condition
referred to as cretinism (stunted physical and mental growth
What is the happening in Grave’s disease
In Graves’ disease, your immune system creates antibodies that cause the thyroid to grow and make more thyroid hormone than your body needs. These antibodies are called thyroid-stimulating immunoglobulins (TSIs). The TSIs bind to thyroid cell receptors, which are normally “docking stations” for thyroid-stimulating hormone (TSH—the hormone responsible for telling the thyroid to produce hormones). The TSIs then trick the thyroid into growing and producing too much thyroid hormone, leading to hyperthyroidism.
How grave’s disease is treated
With radioactove iodine to destroy thyroid cells
2 major classes of hormones and their examples
Hydrophilic hormones: are water soluble. Most are peptide or
protein hormones. Ex=insulin from the pancreas or
catecholamines (adrenal hormones) eg. epinephrine
• Lipophilic hormones: Have a high lipid solubility and are
poorly soluble in water.
include thyroid hormone and steroids
3 classes of hormones based on their derivative
peptide
steroid
amine(tyrosine)
Peptide and amine hormones are made and stored ___
Made in advance, stored in secretory vesicles
What hormones have long half-life
Steroid and thyroid hormones
All steroids are derived from
Cholesterol
Thyroid hormone is ___ derivative
Iodinated tyrosine
What are tropic hormones and example
target other endocrine glands and
stimulate their growth and secretion of other hormones
ex. ACTH targets the adrenal cortex
Sex hormones target
Reproductive tisues
Anabolic hormones ___(function) and example
stimulate anabolism (to build) in
target cells ex testosterone stimulates protein synthesis
and build up of cellular tissue, especially in muscle
The solubility properties of a hormone determine
1. The way the hormone is transported in the blood 2. The mechanism by which the hormone exerts its effect-signaling 3. The means by which the hormone is processed by the endocrine cell
Hydrophilic hormones are transported ___ and lipophylic hormones are transported ___
Hydrophilic hormones are dissolved in the plasma.
• Most lipophilic hormones are bound reversibly to plasma
proteins. These hormones are released by these proteins when
they actively signal target cells
What is the usual action of hormones
Hormones generally produce their effect by altering intracellular
proteins
Binding to receptors hydrophilic vs lipophilic
Hydrophilic hormones bind to receptors on the surface of
target cells.
• Lipophilic hormones pass through target cell membranes and
bind to receptors inside the target cell.
Precursors of hydrophilic hormones are
Prehormones
Where prehormones made
They are made on ribosomes of the ER. In the Golgi complex they
are converted to prohormones by chopping off peptide fragements by enzymes and, finally, active hormones. The
Golgi complex concentrates these hormone into secretory vesicles, and released by exocytosis
Cholesterol derived hormone are not ___
Only the precursor (cholesterol) is stored. The
lipid-soluble hormone is not stored (metabolized by liver) or
excreted in urine
All steroid hormones have what in the structure
4 fused rings
Where lipophylic hormones binds
bind receptor which usually
has zinc finger DNA binding domain, bind at HRE
(hormone response elements) to initiate gene
transcription.
Steroid hormones
cortisol (adrenals), aldosterone (adrenals),
estrogen (ovary and testis), progesterone (ovary-
CL), and testosterone (testis-Leydig cells)
Non-steroid hormones are synthesized from
AAs
Insulin is the example of what structure of protein
long, folded chains of
amino acids;
Example of glycoprotein hormones
hCG (human chorionic hormone-pregnancy recognition)
Peptide hormones- structure and examples
smaller than protein hormones;
short chain of amino acids; e.g., oxytocin and antidiuretic
hormone (ADH)
How amine hormones are synthesized and they are produced by
synthesized by modifying a single molecule
of tyrosine; produced by neurosecretory cells and by neurons;
Example of amine hormones
epinephrine and norepinephrine (adrenal medulla)
General principles of hormone action
Hormones signal a cell by
binding to the target cell’s
specific receptors in a
“lock-and-key” mechanism
What are three hormone actions that work together
Synergism
Permissiveness
Antagonism
What is synergism and example
combinations of hormones acting together have a
greater effect on a target cell than the sum of the effects that
each would have if acting alone (ex FSH and estrogen act on
granulosa cells)
What is permissiveness
when a small amount of one hormone permits,
or enables,a second one to have its full effects on a target cell
Nam example of antagonism
parathyroid hormone {increase blood Ca2+}
and calcitonin {thyroid decrease blood Ca2+).
Why it is important to terminate hormone action and how it is done
insulin secretion when blood glucose is high
following a meal
- As long as insulin is present, glucose taken up by cells
- Extended actions of insulin would deprive the brain
of glucose
- Regulated by terminating hormone activities
- Hormones have a half-life and are degraded into
inactive metabolites in the liver which are then
excreted
What is mobile-receptor model
hormone passes into nucleus, where it binds to
mobile receptor and activates a certain gene sequence to begin transcription
of mRNA; newly formed mRNA molecules move into the cytosol, associate
with ribosomes, and begin synthesizing protein molecules that produce the
effects of the hormone
The amount of steroid hormone determine
magnitude of a target
cell’s response
Why steroid response is slow
transcription and protein synthesis take time
Sensitivity of the cell depends on
number of receptors
that cell has
Why it is important to break down and replace hormone receptors
This process not only provides new receptors but also a level of
control where new receptors can be incorporated and
transcription increased
What is up-regulation and down-regulation
Up-regulation—increased number of hormone receptors
increases sensitivity-hormones often regulate own receptor levels
– Down-regulation—decreased number of hormone receptors
decreases sensitivity
How second messenger mechanism differs from steroid hormone action
- Effects of the hormone are amplified by the cascade of
reactions
-due to this cascade the effects can be disproportionately great
when compared to the amount of hormone present (ex 10
cAMP)
2.The second messenger mechanism operates much more quickly
than the steroid mechanism
Who usually acts through second messenger mechanism
Nonsteroid hormones
Action of GPCR and adenylyl cyclase
When a GPCR is activated by its extracellular ligand, a conformational change is induced
In a cAMP-dependent pathway, the activated Gs alpha subunit binds to and activates an enzyme called adenylyl cyclase, which, in turn, catalyzes the conversion of ATP into cyclic adenosine monophosphate (cAMP)-second messenger
cAMP activates protein kinase A, which phosphorylated proteins, which brings cellular response
What hormone acts through GPCR and adenylyl cyclase
FSH-follicle stimulating hormone
Some cells use ___ instead of cAMP. In that case ___ is not activated, but ___
Ca
In this case there is still binding of G-protein linked receptor in
the membrane but instead of activation of Adenyl Cyclase,
Phospholipase C is activated.
Function of GPCR through IP3
The extracellular signal molecule binds with the G-protein receptor (Gq) on the cell surface and activates phospholipase C, which is located on the plasma membrane. The lipase hydrolyzes (PIP2) into two second messengers: (IP3) and (DAG). IP3 binds with the IP3 receptor in the membrane of the smooth endoplasmic reticulum and mitochondria to open Ca2+ channels. DAG helps activate protein kinase C (PKC), which phosphorylates many other proteins, changing their catalytic activities, leading to cellular responses.
What is the common feature of hormonal control
Negative feedback control
Example of feedback loop with thyroid hormone
1. Plasma concentration of thyroid hormone falls (ex T3 and T4) 2. the anterior pituitary secretes TSH 3. thyroid in turn secretes TH 4.TH inhibits further secretion TSH
Parathyroid hormone controls
Blood calcium concentrations-> increases it
What is happening with PTH during lactation
Due to lactation blood Ca concentration is lowered. • This change is sensed and responded to by the parathyroid • Parathyroid increases secretion of parathyroid hormone (PTH). • PTH stimulates osteoclasts in bone to release more Ca++ from storage in bone tissue • which increases maternal blood Ca++ concentration to the set point level.
Size of pituitary gland
- 2 to 1.5 cm
0. 5 g in weight
What part connects pituitary gland to the hypothalamus
Infundibulum
Anterior and posterior parts of pituitary gland
Anterior-adenohypophysis
Posterior-Neurohypophysis
What is the purpose of portal vessels in anterior pituitary
Neurons in hypothalamus secrete trophic hormones that are carried directly to anterior pituitary through portal vessels
Adenohypophysis (anterior pituitary) divides into
• Pars anterior—forms the major portion of
adenohypophysis
• Pars intermedia
Tissue in adenohypophysis is composed of
irregular clumps of secretory
cells supported by fine connective tissue fibers and
surrounded by a rich vascular network
5 types of secretory cells in pituitary
- Somatotrophs
- Corticotrophs
- Thyrotrophs
- Lactotrophs
- Gonadotrophs
Role of somatotrophs
secrete GH (growth hormone,aka somatotropin)
Role of corticotrophs
secrete ACTH (adrenocroticotropic hormone) and MSH
Role of thyrotrophs
secrete TSH (thyroid stimulating hormone)
Role of lactotrophs
secrete prolactin (PRL)
Role of gonadotrophs
secrete LH (luteinizing hormone) and FSH (follicle stimulating hormone)
How growth hormone actions
promotes growth by stimulating the liver to produce
growth factors which in turn accelerates amino acid
transport into cells.
• Promotes growth of bone, muscle, and other
tissues by accelerating amino acid transport into
the cells-all process involve protein anabolism
• GH also stimulates lipid metabolism
- accelerates mobilization of lipids from cells and
speeds up lipid catabolism. This essentially shifts a
cells use of nutrients from glucose catabolism to
lipid catabolism
-Has also hyperglycemic affect
GH and insulin have ___
Opposite effects
GH affects metabolism in 3 ways
promotes protein anabolism
- promotes lipid mobilization and catabolization
- Indirectly inhibits glucose metabolism by shifting energy use
to lipid catabolism
- indirectly increases blood glucose
Another name for GH
Insulin-like growth factor
4 principle tropic hormones
- Thyroid stimulating
- Adrenocorticotropic
- Follicle-stimulating
- Luteinizing
Control of anterior pituitary happens through
Negative feedback form hypothalamus
What happens with FSH at menopause
Increase, higher than LH, so no corpus luteum-> The corpus luteum is essential for establishing and maintaining pregnancy in females.
What is hypothalmichypophyseal
portal system
This is a capillary to capillary connection
Blood in this system carries
hypothalamic signals directly to the anterior pituitary
Role of hypophyseal portal system
carries blood from
hypothalamus directly to adenohypophysis where target
cells of releasing hormones are located
Hormones secreted by hypothalamus that are controlling pituitaru
Growth hormone releasing hormone (GHRH)
- Growth hormone inhibiting hormone(GHIH)
- Corticotropin releasing hormone (CRH)
- Thyrotropin-releasing hormone (TRH)
- Gonadotropin-releasing hormone (GnRH)
- Prolactin releasing hormone (PRH)
- Prolactin inhibiting hormone (PIH)
Relationship between the hypothalamus
and posterior pituitary (neurohypophysis)
Neurosecretory cells have their bodies directly in the hypothalamus and their axon terminals in the posterior pituitary. • Posterior pituitary releases oxytocin and vasopressin (ADH)
3 hormone pathologies
- Hormone excess
- Hormone deficiency
- Abnormal responsiveness of target tissues
Cushing’s disease is
hypercortisol secretion
Describe cushing’s disease
Normal cortisol action: 1.Protein breakdown 2.Glucose formation 3.Lipolysis 4.Anti-inflammatory effects 5.Depression of immune responses •Hypersecretion exagerate`s a hormone`s effects
Symptoms: breakdown of muscle proteins and redistribution of body fat, resulting
in spindly arms and legs accompanied by a rounded moon face, pendulous
abdomen, flushed appearance
Cushing’s disease is caused
tumour of adrenal gland secreting cortisol, or a tumour elsewhere
secreting ACTH, which in turn stimulates excessive secretion of cortisol
Normal actions of thyroid gland
1.Increase basal metabolic rate: stimulates the use of oxygen to
produce ATP
2.Calorigenic effect: stimulates synthesis of additional
sodium-potassium ATPase
3.Stimulate protein synthesis and increase use of glucose and
fatty acids for ATP production
4.Enhance actions of catecholamines
5.Accelerate body growth
Hypothyroid secretion symptoms and causes
Symptoms: swelling of facial tissues (puffiness), slow heart rate,
low body temperature, senstivity to cold, dry hair and skin
•Causes: iodine deficiency, stress, congenital (rare)
Normal insulin action
- Accelerate facilitated diffusion of glucose into cells
- Speed conversion of glucose into glycogen
- Increase uptake of amino acids and increase protein synthesis
- Speed synthesis of fatty acids (lipogenesis)
- Slows glycogenolysis
- Slows gluconeogenesis
Causes of abnormal response to insulin and symptoms
•Causes:obesity
• •Symptoms: high blood glucose, weight loss, excessive
thirst, frequent urination
What is happening in DM
Glucose is not uptaken by cells
What hormones balance calcium in use
Calcitonin, parathyroid hormone, and vitamin D
