ENDOCRINOLOGY Flashcards
- the study of hormones & their actions
ENDOCRINOLOGY
- tissues that release their secretory products into extracellular & interstitial fluids
ENDOCRINE GLANDS
- a finely integrated system whereby the hypothalamus, pituitary & target glands continually communicate through feedback inhibition & stimulation, to control all aspects of metabolism, growth and reproduction (Henry)
ENDOCRINE SYSTEM
- secretory products transported in the bloodstream from their place of synthesis to a distant location where they exert their action
HORMONES
Some hormones also act in close proximity to their
site of release
What are hormones? Substances secreted by an endocrine gland and transported in the blood that…
1) Control rates of certain chemical reactions
2) Transport substances across cell membranes
3) Help regulate water and electrolyte balance
4) Play a role in reproduction
1) Control rates of certain chemical reactions ex
Thyroid hormones
2) Transport substances across cell membranes
Insulin
3) Help regulate water and electrolyte balance
Aldosterone
ADH
4) Play a role in reproduction ex
Estrogen (F)
Testosterone (M)
Follicle-stimulating hormone (M & F)
Three general classes of hormones
- STEROIDS
- POLYPEPTIDES & PROTEINS
- HORMONES DERIVED FROM AMINO ACIDS
Water-insoluble
- STEROIDS
Water-soluble
- POLYPEPTIDES & PROTEINS
- HORMONES DERIVED FROM AMINO ACIDS
Hydrophilic
- POLYPEPTIDES & PROTEINS
- HORMONES DERIVED FROM AMINO ACIDS
Hydrophobic
- STEROIDS
Most are proteinbound
- STEROIDS
Most are free
- POLYPEPTIDES & PROTEINS
Some are free (50%)
The rest are bound
- HORMONES DERIVED FROM AMINO ACIDS
- STEROIDS Half-life:
60 - 100 mins
- POLYPEPTIDES & PROTEINS Half-life:
vary from 5 to 60 mins.
- HORMONES DERIVED FROM AMINO ACIDS
Thyroxine - proteinbound (Half-life: ?)
Epinephrine - not protein-bound (Halflife: ?.)
almost 1 week
<1 min
Nuclear receptor
Cell membrane receptor
STEROIDS aka
Steroid hormones
HORMONES DERIVED FROM AMINO ACIDS aka
Non-steroid hormones
generally hydrophobic
STEROIDS
Many circulate in plasma bound to high-affinity proteins
STEROIDS
Small % are free for biologic activity
STEROIDS
Formed from cholesterol
Steroid Hormones
Can-pass through cell membranes.
Steroid Hormones
Receptors for steroid hormones are located in the
target cell’s nucleus
The H-R complex binds with the DNA and activates specific genes that, in turn, direct the synthesis of specific proteins.
Steroid Hormones
water-soluble (Hydrophilic)
POLYPEPTIDES & PROTEINS
HORMONES DERIVED FROM AMINO ACIDS
Circulate unbound in plasma (freely)
POLYPEPTIDES & PROTEINS
Initiate their response by binding to cell membrane receptor
POLYPEPTIDES & PROTEINS
Either free or protein-bound
HORMONES DERIVED FROM AMINO ACIDS
Half-lives vary
HORMONES DERIVED FROM AMINO ACIDS
Initiate their response by binding to cell membrane receptor ex
Insulin
PTH
Adrenocorticotropic hormone
HORMONES DERIVED FROM AMINO ACIDS ex
Thyroxine
Epinephrine
Hormones possess a high degree of
structural specificity
between hormone and receptor
1:1
Slight alteration in molecular composition may bring significant
changes in
physiological activity
FUNCTIONS OF HORMONES
THREE GENERAL ASPECTS:
I. REGULATORY FUNCTION
• Maintain constancy of chemical composition of ECF & ICF
I. REGULATORY FUNCTION
II. MORPHOGENESIS
III. INTEGRATIVE ACTION
Other regulatory functions:
• Responses to demands of:
o Starvation
o Infection
o Trauma
o Psychological stress
o Process of sexual reproduction
• Control the growth & development of an organism
II. MORPHOGENESIS
• Control the growth & development of an organism ex
o Testosterone
o Estradiol
o GH: influences devt of male and female characs
o Testosterone
o Estradiol
• Most complex & the least understood
III. INTEGRATIVE ACTION
• Several endocrine hormones may be important for regulating a single function
III. INTEGRATIVE ACTION
Types of Hormone Action according to Tietz
- Endocrine
- Neuroendocrine
- Neurocrine
- Neurotransmission
- Paracrine
- Exocrine
hormone synthesized in one location & released into plasma
- Endocrine
Binds to specific receptors in cells at a distant site to elicit characteristic response
- Endocrine
Hormone action (gardner-shoback)
- PARACRINE
- AUTOCRINE
- INTRACRINE
- JUXTACRINE
Endocrine ex
TSH
Neurocrine ex
Norepinephrine
Paracrine ex
Somatostatin
Exocrine ex
Gastrin
hormone synthesized in nerve ending & released into EC space
Neuroendocrine
Interacts w/ receptors of cells at distant site
Neuroendocrine
hormone synthesized in neurons & released into EC space
Neurocrine
Binds to receptor in nearby cell & affects its function
Neurocrine
hormone synthesized in neurons & released from nerve endings
Neurotransmission
Crosses synapse & binds to specific receptors in another neuron
Neurotransmission
hormone synthesized in endocrine cells & released into EC space
Paracrine
Binds to specific receptor of nearby cell & affects its function
Paracrine
hormone synthesized in endocrine cells & released into lumen of gut
Exocrine
- acts on neighboring cells
PARACRINE
counterpart ex: Somatostatin
PARACRINE
– hormone acts on receptors found on the same cell; “self”
AUTOCRINE
- related to autocrine; hormone will not be released by the cell
INTRACRINE
- hormone bound on one cell but interacts w/ a receptor on a diff cell
JUXTACRINE
The biological response to a hormone is initiated by the binding of the hormone to
target cell receptors
- provides the target cell with a mechanism for recognizing & concentrating the hormone
RECEPTOR
- activates the target cell to begin the chain of events that constitutes the biological effect(s) of that hormone
H - R complex
CHARACTERISTICS OF THE H- RCOMPLEX
- Highly specific
- An equilibrium system
- It has high affinity
- It is saturable
• The degree of biological response of a target fissue is
directly proportional to the # of H-R complexes
- It is saturable
• Maximal response is obtained when all sites are filled
- It is saturable
Main function of the Endocrine System:
Secretion of hormones to be released in the circulation
3 WAYS TO CONTROL OF HORMONAL SECRETIONS
- Releasing (trophic) hormones from the HYPOTHALAMUS control secretions of the anterior pituitary.
- The NERVOUS SYSTEM influences certain endocrine glands directly.
- FREE-STANDING GLANDS: respond directly to changes in fluid composition.
- Releasing (trophic) hormones from the [?] control secretions of the anterior pituitary.
HYPOTHALAMUS
- The [?]influences certain endocrine glands directly.
NERVOUS SYSTEM
FREE-STANDING GLANDS
Releasing (trophic) hormones from the HYPOTHALAMUS control secretions of the anterior pituitary ex
Tyrotrophin-releasing hormone
FREE-STANDING GLANDS ex
Parathyroid gland secreted by the Parathyroid hormone
An increase in one hormone would result in the increase of a second hormone
Positive feedback
more commonly observed
Positive feedback
An increase in one hormone causes a decrease in the second hormone
Negative feedback
• First endocrine gland
HYPOTHALAMUS
HYPOTHALAMUS
Located [?]
behind the frontal lobe and below the thalamus
Regulates anterior pituitary hormonal secretion
HYPOTHALAMUS
HYPOTHALAMUS 7 hormones :
3 regulatory hormones
2 pairs of regulatory and inhibitory hormones
TRH (thyrotrophin-releasing hormone)
HYPOTHALAMIC HORMONE
TSH (Thyroid-stimulating hormone)
ANT. PITUITARY HORMONE
CRH (corticotrophin-releasing hormone)
HYPOTHALAMIC HORMONE
ACTH (Adrenocorticotropic hormone)
ANT. PITUITARY HORMONE
GnRH (gonadotrophin-releasing hormone)
HYPOTHALAMIC HORMONE
LH (Luteinizing hormone) and FSH (Follicle-stimulating hormone)
ANT. PITUITARY HORMONE
GHRH (growth hormonereleasing hormone)
HYPOTHALAMIC HORMONE
GH (growth hormone)
ANT. PITUITARY HORMONE
Somatostatin (GHRH counterpart)
HYPOTHALAMIC HORMONE
Suppress GH
Somatostatin
Suppress PRL
PIF
PRF (prolactin-releasing factor)
HYPOTHALAMIC HORMONE
PRL
ANT. PITUITARY HORMONE
PIF (prolactininhibiting factor)
HYPOTHALAMIC HORMONE
3 important regulatory hormones:
• TRH • CRH • GnRH
GHRH counterpart
Somatostatin
Dopamine
PIF
PRF counterpart
PIF
prolactin
PRL
PIF counterpart
PRL
HYPOTHALAMIC HORMONE
Regulates TSH secretion
TRH
TRH-secreting neurons are located in the
medial portions of the PVN
Known as a tripeptide (consists of 3 amino acids)
TRH
TRH Innervated by axons that release:
Norepinephrine
Leptin
‘Neuropeptide Y
Somatostatin
Secretion is influenced by energy state and temperature
TRH
• Stimulates secretion of ACTH and other products of its precursor molecule
CRH
CRH-secreting neurons are found in the
anterior portion of the PVN (paraventricular nucleus)
• Stimulates LH and FSH secretion
GnRH
GnRH Neurons are primarily located primarily in the
preoptic area of the hypothalamus
Neuron carriers are said to be unusual
GnRH
GnRH Stimulated by:
GALP (galanin-like peptide)
Kisspeptine
Norepinephrine
GnRH Inhibited by:
GABA (gamma-aminobutyric acid)
Endorphine
CRH
• Stimulates GH secretion by somatotrophs
GHRH
• GHRH Neurons are located in the
arcuate nuclei of the medial basal hypothalamus
• GHRH Stimulated by:
- Dopamine
- Galanine
- Brain stem neurons
• GHRH Suppressed by:
SRIH (somatostatin release-inhibiting hormone)
• Suppress secretion of GH and TRH (thyrotrophin-releasing hormone)
Somatostatin
Somatostatin Neurons are located in the
periventricular region
• Shows the relationship between the hypothalamus, pituitary gland, and the target organ
Hypothalamic Pituitary Organ Axis (HPO Axis)
TSH
Thyroid
T4 (triodothyroni ne) and T3 (thyroxine)
TRH
ACTH
Adrenal Cortex
Cortisol
CRH
LH, FSH
Ovaries or Testes
Estrogen, Testosterone
GnRH
Pituitary gland a.k.a
hypophysis or master gland
Pituitary gland a.k.a Located within the
sella turcica
Pituitary gland
Connected to the median eminence of the hypothalamus by the
infundibular stalk
HORMONE-SYNTHESIZING & SECRETING CELLS OF THE ANTERIOR PITUITARY GLAND:
- Somatotrophs
- Lactotrophs
- Thyrotrophs
- Gonadotrophs
- Corticotrophs
- secrete GH
Somatotrophs
Responds to GH-releasing hormone
Somatotrophs
Inhibited by GH-inhibiting hormone
Somatotrophs
- secrete prolactin (PRL)
Lactotrophs
Responds to thyrotrophin-releasing hormone, prolactinreleasing hormone, and dopamine
Lactotrophs
- secrete thyroid-stimulating hormone (TSH)
Thyrotrophs
Responds to thyrotrophin-releasing hormone
Thyrotrophs
- secrete a- and B-subunits of FSH & LH
Gonadotrophs
Responds to gonadotrophin-releasing hormone
Gonadotrophs
- secrete pro-opiomelanocortin (POMC)
Corticotrophs
Responds to corticotrophin-releasing hormone
Corticotrophs
pro-opiomelanocortin: precursor to ACTH
Corticotrophs
Main Target Organs of the Anterior Pituitary tropic hormones:
• Thyroid gland
• Adrenal cortex
• Gonads
Most abundant hormone in the anterior pituitary gland
Human Growth Hormone
Marked structural resemblance to PRL & hCS
Human Growth Hormone
(?): helps during pregnancy
placental hormone chorionic somatomammotropin (hCS)
Human Growth Hormone
Concentration varies with[?]
exercise sleep and stressional status
Human Growth Hormone Peak levels occur [?] after the onset of sleep
1 - 4 hrs
Locations of Receptors of the Human Growth Hormone
- Liver
- Bones
- Adipose tissue
- Muscle
Human Growth Hormone
Promote growth of [?] by stimulating protein synthesis
cartilage, bone & many soft tissues
Human Growth Hormone
Growth-promoting effects mediated by IGF-1 (aka [?])
Somatomedin C
Stimulation:
Deep sleep
a-Adrenergic
Fasting
Acetylcholine
Sex steroids
Stress
Amino acids
Hypoglycemia
Ghrelin
Opiods
Suppression:
Obesity
B-Adrenergic
Glucocorticoids
High FFA
Hyperglycemia
Hypothyroidism
Elevated IGF-1
Inhibition:
Undernutrition
Acute illness
Chronic illness
GH receptor deficiency
GHR antibodies
IGF-I receptor deficiency (genetic)
Insulin like activity in other tissues
igfS
Enhances synthesis of collagen and proteoglycans
igfS
Affects positively calcium, magnesium and potassium homeostasis
igfS
Concentration rise during childhood
igfS
Achieve peak conc. During puberty
igfS
GH affects the bone and cartilage directly through [?]
IGFs
Increase in growth of soft tissue and skeleton is accompanied by changes in[?]
electrolyte metabolism
Increase intestinal absorption of [?]
calcium
Decreased urinary excretion of [?]
sodium and potassium
Increases [?]
blood glucose
Insulin [?]
antagonist
GH Reference values:
• Children : generally higher than adults
• Males: 4.2 +/ - 1.2 mg/dL
• Females : 5.1 +/ - 1.0 mg/dL
[?] induce growth in similar manner
GH and Insulin
Their respective effects on glucose homeostasis oppose each other
GH and Insulin
Conditions associated with abnormal release of hormone: Acromegaly
• Pathologic or autonomous
• Caused by pituitary tumor
• Increase width of bone rather than length (hand, feet and jaw)
• Generalized organomegaly and coarsening of facial features
• hyperglycemia
Diagnosis for acromegaly
Randomly collected [?]
IGF-1
Tests for acromegaly
• Screening test
• Oral glucose tolerance test
• Confirmatory test
Oral glucose tolerance test
Oral glucose tolerance test
Obtain baseline blood sample for
glucose and GH
Oral glucose tolerance test
Administering [?] of glucose orally, obtain blood for glucose and GH every [?] over the next [?]
75 g
30 mins
2 hours
Oral glucose tolerance test
Normal response: suppression of GH to [?] at anytime of the day
< 1 ng/mL
GH deficiency/ primary dwarfism
Children: idiopathic GH deficiency
Adults : pituitary adenoma
Gold standard test
INSULIN TOLERANCE TEST
Failure of blood sugar level to decrease in response to insulin
INSULIN TOLERANCE TEST
• Synthesized in thyrotrophs
Thyroid stimulating hormone
• Composed of two non-covalently linked alpha & beta sub-units
Thyroid stimulating hormone
a-unit is identical to [?]
FSH, LH & hCG
B-unit attaches to
thyroid receptors
B-unit attaches to thyroid receptors & stimulate:
Stimulates growth and vasculature of the thyroid gland
Uptake and organification of iodine
Promotes release of stored thyroid hormones
Thyroid Stimulating Hormone Test
Immunoradiometric assay (IRMA)
Ultrasensitive
Immunoradiometric assay (IRMA)
best thyroid function test
Immunoradiometric assay (IRMA)
Differentiate hypo vs hyperthyroidism
Thyroid Stimulating Hormone
Immunoradiometric assay (IRMA)
• detectable in the serum of thyrotoxic patients which imitates the biologic action of TSH
LATS (long acting thyroid stimulating substance)
Produced by thyroid gland
T3, T4: controls rate of reaction
TSH
Thyroid hormones
Produced by pancreas in response to high of glucose plasma level
Insulin
Transports glucose extracellular to intracellular
Insulin
Promotes reabsorption of water and electrolyte balance
Aldosterone
ADH
Water-fearing; Formed from cholesterol - insoluble to water
STEROIDS
Location: nucleus; Differentiate one type of hormone to another
Steroid Hormones
H-R complex
Hormone-receptor complex
Receptor in the cell membrane
Steroid Hormones
End result: Formation of a specific protein
Steroid Hormones
Steroid is hydrophobic - passively enters the cell (passive diffusion)
steroid hormones
Traverse the cell cytoplasm and directly enter the cell nucleus where the receptor is located
steroid hormones
o Yellow: hormone
o Purple: receptor
steroid hormones
Formation of the Hormone-receptor complex affecting the DNA
steroid hormones
Activates specific genes that direct synthesis of specific proteins
steroid hormones
Less complicated (direct impact on DNA)
steroid hormones
steroid hormones
End result:
Formation of a specific protein
Small circle:
nonsteroid hormones
Hormones derived from protein or amino acid
nonsteroid hormones
Soluble
nonsteroid hormones
Receptor in the cell membrane
nonsteroid hormones
Binding forms H-R complex; Cascade of biological activity takes place
nonsteroid hormones
nonsteroid hormones
H-R complex activates [?] connected to the receptor
G protein activates [?]
Adenylate Cyclase moves 2 phosphates from [?] (substrate) to produce [?] (product)
G protein
Adenylate Cyclase
ATP; Cyclic Adenosine Monophosphate
- secondary messenger that affects biological processes; activates inactive form
Cyclic Adenosine Monophosphate (cAMP)
More complicated (there are still enzymes to be activated)
nonsteroid hormones
nonsteroid hormones
End result:
Cellular change
Maintain constancy of chemical composition of ECF & ICF
Thru regulation of [?]
salt, water, proteins, fats, and carbohydrates
Receptors found on distant sites
Endocrine
TSH
Produced by anterior pituitary gland or base of the brain
Released in the plasma to reach the thyroid
Endocrine
has a significant effect of the cardiac muscle cells
Norepinephrine
secreted by nerve endings and receptor is nearby its site of origin
Norepinephrine
produced by the pancreas
Somatostatin
action on a different cell of the pancreas
Somatostatin
secreted by the delta cell of the islet of the pancreas
Somatostatin
action on the beta cell and alpha cell
Somatostatin
Outside the circulation
Exocrine
Secretion of gastric juice; Mucosal cells; Helps in the metabolism of food
Gastrin
Allows the target tissues to recognize many mol to w/c it is exposed to
It has high affinity
Stimulates pituitary gland to release thyroidstimulating hormone
Tyrotrophin-releasing hormone
Made of [?] serving as building blocks of communication
neurons
Certain stimuli directs neurons to send signals to the brain (?)
hypothalamus
Acts on the bones and kidneys to regulate serumcalcium concentration
Parathyroid gland secreted by the Parathyroid hormone
Releasing hormone:
Hypothalamus
Tropic hormone:
Pituitary gland
Effector hormone:
Gland
more commonly observed
Positive feedback
– part of the brain involved in the storage of longterm memory
Hippocampus
Hippocampus sends signal to the hypothalamus to release
corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP)
corticotropin-releasing hormone (CRH) acts on the anterior pituitary gland to secrete
adrenocorticotropic hormone (ACTH)
adrenocorticotropic hormone (ACTH) stimulates
glucocorticoids (cortisol)
– stress hormone; stimulates the body to make use of the remaining energy; effect is stress eating
cortisol
Excessive levels of glucocorticoids in the blood or cortisol in the plasma will send signal to the anterior pituitary gland to stop ACTH production and hypothalamus to stop CRH production
Negative feedback
Responds to levels of chemicals in the circulation
FREE-STANDING GLANDS
FREE-STANDING GLANDS ex
Parathyroid hormone (PTH)
Decreased level of calcium trigger the free-standing gland (PT gland) to release [?]
PTH
[?] acts on bones and kidneys to release calcium
PTH
Once corrected, it will signal the free-standing gland to stop [?] production
PTH
Trophic/releasing hormones; effect on the anterior pituitary gland
HYPOTHALAMIC HORMONE
: triggers ovulation
LH
: regulates devt of growth and puberty
FSH
: regulates puberty and reproduction
Kisspeptine
Pituitary gland
Located in the
base portion of the skull
: depression that encloses the pituitary gland
Sella turcica
Sella turcica structure
Turkish saddle (seat of a bike)
: sac-like structure
Pituitary gland
: tube-like structure that connects the hypothalamus and pituitary gland
Infundibular/Pituitary stalk
Two distinct regions of the pituitary gland:
Anterior portion and Posterior portion
Pituitary gland
Secretes [?] different peptides and protein hormones
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Anterior pituitary gland aka
adenohypophysis
Surrounded by a capillary network that extends from hypothalamus down to the infundibulum and the pituitary gland
Anterior pituitary gland (adenohypophysis)
Synthesizes and secretes seven hormones
Anterior pituitary gland (adenohypophysis)
Contains different types of cells; Each cells synthesizes and secretes specific hormones upon the stimulation of trophic hormones from the hypothalamus
Anterior pituitary gland (adenohypophysis)
Two types of chromophils:
Pink: acidoohilic
Blue/purple: basophilic
Pink: acidoohilic
- Somatotrophs
- Lactotrophs
Blue/purple: basophilic
- Corticotrophs
- Thyrotrophs
- Gonadothrophs
Conc of human GH rises [?] after a meal and a physical activity
3 hrs
is a stimulant for GH secretion
Stress
Peak of GH secretion happens during the
deepest sleep
Primary receptor of human GH is found in the
liver
Liver secretes a group of polypeptide hormone called
Insulin-Growth Factor 1 (IGF-1)
Secretion of human GH is stimulated by [?] from the hypothalamus, which is inhibited by somatostatin hormone growth inhibiting hormone
GHRH
Pituitary gland again release [?], traveling to the circulation, then reach its target receptor (primary: liver)
GH
Liver is triggered to secrete
IGF-1
[?] directly affects the long bones and muscle by helping in its growth and devt
IGF-1
Other receptors are found in [?], triggering catabolism or lipolysis
adipose tissues
: decreases blood sugar by carrying glucose in the plasma inside the cells
Insulin-like GF
Gives rigidity and support to to skin
collagen and proteoglycans
igfS
Achieve peak conc. During puberty
13 to 15 yrs old
One effect of igfS is
bone resorption
Bones and osteoblasts releases their contents/electrolytes
bone resorption
Insulin antagonist
Side effect: stimulates [?] (prod of glucose from noncarbohydrate sources) and [?] (lysis of glycogen)
glucogeneolysis
glycogeneolysis
: disorder of IGF-1 which causes excessive growth of the hands, feet, jaw, and internal organs in adulthood
Acromegaly
Growth is straight; childhood
Acromegaly
: abnormally high linear growth due to the excessive action of IGF-1 before the closure of the epiphyseal growth plates in childhood
Gigantism
Growth upwards; childhood
Gigantism
shows a pituitary tumor in 90% of acromegalic patients
MRI
The best confirmatory test for acromegaly is the
oral glucose suppression test
In [?], glucose does not suppress growth hormone
acromegaly
Decreases from the baseline; Failure to decrease is diagnostic of acromegaly; Collection: 5x
Oral glucose tolerance test
Damage to the pituitary gland or the hypothalamus
idiopathic GH deficiency
Tumor or cancer
pituitary adenoma
: psychosocial dwarfism (due to stressful environment)
Secondary dwarfism
Administration of insulin via IV following an overnight fasting
INSULIN TOLERANCE TEST
Collection of blood sample every 15, 30, 60,.. minutes
INSULIN TOLERANCE TEST
Goof indicator of GH deficiency/ primary dwarfism
INSULIN TOLERANCE TEST
Ag and Ab + radioisotope; Measurement of radioactivity
Immunoradiometric assay (IRMA)
