Endocrine Physiology - BRS & Guyton and Hall Flashcards
ADH
- Originates primarily in supraoptic nuclei of hypothalamus
- Inc. H2O permeability (aquaporin 2, AQP2) of principal cells of late distal tubule and collecting duct (via V2 receptor and adenylate cyclase-cAMP mech)
- Constriction of vsm (via V1 receptor and IP3/Ca2+ mech)
Aldosterone
Inc. renal Na+ reabsorption
Inc. renal K+ secretion
Inc. renal H+ secretion
Under tonic control by ACTH but separately regulated by RAAS and K+
Decrease in blood volume –> dec. renal perfusion pressure –> inc. renin secretion –> catalyzes A to AI –> AI to AII by ACE –> AII acts on zone glomerulosa of adrenal cortex to inc. conversion of corticosterone to aldosterone –> aldosterone inc. renal Na+ reabsorption, thereby restoring extracellular fluid volume and blood volume to normal
Hyperkalemia increases aldosterone secretion (aldosterone increases renal K+ secretion)
A 41-year-old woman has hypocalcemia, hyperphosphatemia, and decreased urinary phosphate excretion. Injection of PTH causes an increase in urinary cyclic adenosine monophosphate (cAMP). The most likely diagnosis is:
A. Primary hyperparathyroidism B. Vitamin D intoxication C. Vitamin D deficiency D. Hypoparathyroidism after thyroid surgery E. Pseudohypoparathyroidism
D. Hypoparathyroidism after thyroid surgery
- Vitamin D intoxication would cause hypercalcemia
- Vitamin D deficiency would cause hypocalcemia and hypophosphatemia
- Not pseudohypoparathyroidism (defective Gs in kidney and bone causes PTH resistance) b/c corrected by exogenous PTH
A 38-year-old man who has galactorrhea is found to have prolactinoma. He is treated with bromocriptine, which eliminates the galactorrhea. What is the basis for the therapeutic action of bromocriptine?
Bromocriptine = dopamine agonist
Secretion of prolactin by anterior pituitary is tonically inhibited by secretion of dopamine from hypothalamus - thus, dopamine agonist acts just like dopamine (inhibits prolactin secretion)
What function of Sertoli cells mediates negative feedback control of FSH secretion?
Synthesis of inhibin
Note: Leydig cells synthesize testosterone which is aromatized in the ovaries
What substance is derived from pro-opiomelanocortin (POMC)?
ACTH
POMC = parent molecule in anterior pituitary for ACTH and intermediary lob for MSH
MSH, a component of POMC and ACTH, stimulates melatonin production.
Which of the following inhibits the secretion of growth hormone by the anterior pituitary?
a. Sleep
b. Stress
c. Puberty
d. Somatomedins
e. Starvation
f. Hypoglycemia
Somatomedin are generated with GH acts on its target tissues; they inhibit GH secretion by the anterior pituitary, both directly and indirectly (by stimulating somatostatin release)
What explains the suppression of let down during pregnancy?
Blood levels of estrogen and progesterone are high.
Although high circulating levels of estrogen stimulate prolactin secretion (lactation) doing pregnancy, milk let down is inhibited by progesterone and estrogen.
After birth, progesterone and estrogen levels fall dramatically. Prolactin can then interact with its receptors in the breast, and lactation continues to proceed if initiated by suckling.
Milk let-down via oxytocin is also initiated by suckling.
Which step in steroid hormone biosynthesis, if inhibited, blocks the production of all androgenic compounds but does not block the production of glucocorticoids?
Conversion of 17-hydroxypregnenolone to dehydroepiandrosterone (as well as conversion of 17-hydroxyprogesterone to androstenedione) is catalyzed by 17,20-lyase.
If this process is inhibited, synthesis of androgens is stopped.
A 46-year-old woman has hirsutism, hyperglycemia, obesity, muscle wasting, and increased circulating levels of ACTH. The most likely cause of her symptoms is:
a. primary adrenocortical insufficiency (Addison’s disease)
b. primary overproduction of ACTH (Cushing’s disease)
d. treatment with exogenous glucocorticoids
b. Cushing’s disease
- Elevation of ACTH stimulates overproduction of glucocorticoids and androgens
Treatment with exogenous glucocorticoids would produce similar symptoms but you would get decreased levels of ACTH b/c of negative feedback.
Addison’s would produce high levels of ACTH due to loss of negative feedback inhibition but symptoms would be of glucocorticoid deficit, not excess.
Cushing’s disease vs. syndrome
Disease - pituitary issue causing over secretion of ACTH –> high levels of cortisol
Syndrome - high levels of cortisol but exerts negative feedback on pituitary to result in low levels of ACTH
Use dex suppression test to distinguish… if you give high levels of dex, and ACTH levels decrease –> Cushing’s disease
Blood levels of which of the following substances is decreased in Graves’ disease?
a. Triiodothyronine (T3)
b. Thyroxine (T4)
c. Diiodotyrosine (DIT)
d. TSH
e. Iodide (I-)
In Graves’ disease (hyperthyroidism), the thyroid is stimulated to produce and secrete high levels of thyroid hormones as a result of stimulation by thyroid-stimulating Igs [antibodies to TSH receptors on thyroid gland]
B/c of high circulating levels of thyroid hormones, anterior pituitary secretion of TSH will be turned off (negative feedback).
Which step in steroid hormone biosynthesis is stimulated by ACTH?
Cholesterol –> pregnenolone
The source of estrogen during the second and third trimesters of pregnancy?
Fetal adrenal gland synthesizes DHEA-S, which is hydroxylated in fetal liver, and then transferred to placenta, where it is aromatized to estrogen
In the first trimester, CL is the source of both estrogen and progesterone
Secretion of oxytocin is increased by:
a. milk ejection
b. dilation of the cervix
c. increased prolactin levels
d. increased ECF volume
e. increased serum osmolarity
b. Suckling and dilation of cervix = stimuli for oxytocin secretion
Milk let-down = RESULT of oxytocin action, not cause of secretion
prolactin secretion is also stimulated by suckling, but prolactin does not directly cause oxytocin secretion
increased ECF and hyperosmolarity = stimuli for other posterior pituitary hormone, ADH
Propylthiouracil can be used to reduce the synthesis of thyroid hormones in hyperthyroidism because it inhibits oxidation of:
a. T3
b. T4
c. DIT
d. TSH
e. Iodide (I-)
E. Iodide
For iodide (I-) to be incorporated into thyroid hormone, it must be oxidized to I2 which is accomplished by a peroxidase enzyme in the thyroid follicular cell membrane. Propylthiouracil inhibits peroxidase and therefore, halts synthesis of thyroid hormones.
A 39-year-old man with untreated DM type I is brought to the ER. An injection of insulin would be expected to cause an increase in his:
a. urine glucose concentration
b. blood glucose concentration
c. blood K+ concentration
d. blood pH
e. breathing rate
DM symptoms pre-insulin:
- Hyperglycemia
- Glycosuria
- Hyperkalemia
- Metabolic acidosis with compensatory hyperventilation
Insulin treatment would decrease blood glucose (by increasing uptake of glucose into cells), decrease urinary glucose (secondary to decreasing blood glucose), decrease blood K+ (shifting K+ into cells), and correct metabolic acidosis (by decreasing production of ketoacids)
Correction in metabolic acidosis will lead to increase in blood pH and will reduce compensatory hyperventilation
What results from the action of PTH on the renal tubule?
Stimulates both renal calcium reabsorption in the renal distal tubule and the 1 alpha-hydroxylase enzyme.
PTH inhibits phosphate reabsorption in the proximal tubule (which is associated with an increase in urinary cAMP).
Which step in steroid hormone biosynthesis occurs in the accessory sex target tissues of the male and is catalyzed by 5alpha-reductase?
Conversion of testosterone –> DHT
A 16-year-old seemingly normal female is diagnosed with androgen insensitivity disorder. She has never had a menstrual cycle and is found to have a blind-ending vagina; no uterus, cervix, or ovaries; a 46 XY genotype; and intraabdominal testes.
Her serum testosterone is elevated. Which of the following characteristics is caused by lack of androgen receptors?
a. 46 XY genotype
b. testes
c. elevated serum testosterone
d. lack of uterus and cervix
e. lack of menstrual cycles
c. elevated serum testosterone is due to lack of AR on anterior pituitary (which normally would mediate negative feedback by testosterone)
presence of testes due to male genotype
lack of uterus and cervix is due to antimullerian hormone (secreted by fetal testes), which suppressed differentiation of the mullein ducts into internal female genital tract
lack of menstrual cycles is due to absence of female reproductive tract
Which hormone stimulates the conversion of testosterone to 17beta-estradiol in ovarian granulosa cells?
Testosterone is synthesized from cholesterol in ovarian theca cells and diffuses to ovarian granulosa cells, where it is converted to estradiol by the action of aromatase (CYP19). FSH stimulates aromatase enzyme and increases the production of estradiol.
Which hormone causes constriction of vsm through an inositol 1,4,5-triphosphate (IP3) second messenger system?
a. ADH
b. aldosterone
c. dopamine
d. oxytocin
e. PTH
ADH causes constriction of vsm by activating V1 receptor that uses IP3 and Ca2+ second messenger system.
When hemorrhage or ECF volume contraction occurs, ADH secretion by posterior pituitary is stimulated via volume receptors. Resulting increase in ADH levels causes increased water reabsorption by collecting ducts (V2R) and vasoconstriction (V1R) to help restore blood pressure
Somatostatin inhibits the secretion of which of the following hormones?
a. ADH
b. Insulin
c. oxytocin
d. prolactin
e. TH
insulin
Somatostatin actions are diverse.
- Secreted by hypothalamus to inhibit GH secretion by anterior pituitary
- Secreted by cells of GI tract to inhibit secretion of GI hormones
- Secreted by delta cells of pancreas to inhibit secretion of insulin and glucagon by beta and alpha cells
Inhibition of which enzyme in the steroid hormone synthetic pathway reduces the size of the prostate?
a. aldosterone synthase
b. aromatase
c. cholesterol desmolase
d. 17,20-lyase (CYP17)
e. 5alpha-reductase
5alpha-reductase catalyzes testosterone –> DHT
DHT = active androgen in several male accessory sex tissues (e.g. prostate)
Seven days after ovulation, pituitary secretion of LH decreases rapidly. What is the cause of this decrease in secretion?
Secretion of estrogen and progesterone by the CL suppresses hypothalamic secretion of GnRH and anterior pituitary secretion of LH.
Which of the following statements about ADH is true?
a. It is synthesized in the posterior pituitary gland.
b. It increases salt and water reabsorption in the collecting tubules and ducts.
c. It stimulates thirst.
d. It has opposite effects on urine and plasma osmolality.
d. It has opposite effects on urine and plasma osmolality.
- Synthesized in supraoptic and paraventricular nuclei of the hypothalamus
- Increases water reabsorption ONLY (hence plasma osmolality dec. while urine osmolality inc.)
- no direct effect on thirst center
A baby is born with a penis, a scrotum with no testes, no vagina, and XX chromosomes. This condition is referred to as hermaphroditism. What could cause this abnormality?
a. The presence of a testosterone-secreting tumor in the mother’s right adrenal gland
b. Abnormally high levels of LH in the material blood
c. Abnormally low rates of estrogen production by the placenta
a. The presence of a testosterone-secreting tumor in the mother’s right adrenal gland
V high conc. of testosterone in a female embryo will induce formation of male genitalia
A young woman is given daily injections of a substance beginning on the 16th day of her normal menstrual cycle and continuing for 3 weeks. As long as the injections continue, she does not menstruate. What could the injected substance be?
HCG has same stimulatory effect as LH on CL.
If you give HCG, the CL will continue to secrete estrogen and progesterone, preventing degradation of the endometrium and onset of menstruation.
Which of the following could inhibit the initiation of labor?
a. Administration of an progesterone antagonist
b. Administration of LH
c. Administration of prostaglandin E2 antagonist
d. Mechanically dilating and stimulating cervix
e. Administration of oxytocin
c. PGE2 strongly stimulates uterine smooth muscle contraction and is formed in increasing rate by the placenta late in gestation
a, d, e - all initiate labor
b. LH no effect
If a radioimmunoassay is properly conducted and the amount of radioactive hormone bound to antibody is low, what would this indicate?
Plasma levels of endogenous hormone are high
What plasma concentrations would you see (aldosterone, cortisol, and potassium) in:
a. a patient with Addison’s disease
b. a patient with Conn’s syndrome
c. a patient on a low-sodium diet
a. a patient with Addison’s disease: secretion of adrenal cortical hormones is deficient –> low levels of aldosterone, low levels of cortisone, increased plasma potassium conc.
b. a patient with Conn’s syndrome: tumors of ZG that secrete large amounts of aldosterone –> high level of aldosterone, low level of plasma potassium (hypokalemia); secretion of cortisol from ZF is normal
c. a patient on a low-sodium diet: high levels of aldosterone; cortisol secretion is normal… although aldosterone increases the rate of potassium secretion by the principal cells of the collecting tubules, this effect is offset by a low distal tubular flow rate. Consequently, there is little change in either potassium excretion or plasma potassium concentration
In order for male differentiation to occur during embryonic development, testosterone must be secreted from the testes. What stimulates the secretion of testosterone during embryonic development?
HCG binds to LH receptors on interstitial cells of testes of male fetus, resulting in the production of testosterone in male fetuses up to the time of birth.
This small secretion of testosterone is what causes the fetus to develop male sex organs instead of female sex organs.
A female athlete who took testosterone-like steroids for several months stopped having normal menstrual cycles. What is the best explanation for this observation?
Testosterone inhibits hypothalamic secretion of GnRH and the pituitary secretion of LH and FSH.
What would you expect in a patient with a genetic deficiency in 11beta-hydroxysteroid dehydrogenase type 2?
a. increased mineralocorticoid activity
b. increased glucocorticoid activity
c. hyperkalemia
d. decreased blood pressure
e. hypoglycemia
a. increased mineralocorticoid activity
the enzyme is present in renal tubular cells and converts cortisol to cortisone, which does not readily bind to mineralocorticoid receptors. When this enzyme is deficient, cortisol, which is present in the plasma in considerably higher concentrations than aldosterone binds the mineralcorticoids receptor and exerts mineralocorticoid effects
mineralocorticoid deficiency: hyperkalemia and decreased BP
During the first few years after menopause, FSH levels are normally extremely high. A 56-year-old woman completed menopause 3 years ago. However, she is found to have low levels of FSH in her blood. Which of the following is the best explanation for this finding?
a. She has been receiving hormone replacement therapy with estrogen and progesterone since she completed menopause.
b. Her adrenal glands continue to produce estrogen.
c. Her ovaries continue to secrete estrogen.
d. She took birth control pills for 20 years before menopause.
a. She has been receiving hormone replacement therapy with estrogen and progesterone since she completed menopause.
After menopause, the absence of feedback inhibition by estrogen and progesterone results in extremely high rates of FSH secretion. Women taking estrogen as part of HRT for symptoms associated w/ postmenopausal conditions have suppressed levels of FSH owing to inhibitory effect of estrogen.
A large dose of insulin is administered intravenously to a patient. What changes, if any, would you expect to see if in terms of GH, glucagon, and epi?
Insulin –> hypoglycemia
Hypoglycemia –> glucagon, GH, epinephrine
During pregnancy, the uterine smooth muscle is quiescent. During the 9th month of gestation, the uterine muscle becomes progressively more excitable. What factors contribute to the increase in excitability?
a. Placental estrogen synthesis rises to high rates
b. Progesterone synthesis by the placenta decreases
c. Uterine blood flow reaches its highest rate
d. PGE2 synthesis by the placenta decreases
e. Activity of the fetus falls to low levels
b. Progesterone synthesis by the placenta decreases
V high levels of progesterone maintain uterine muscle in a quiescent state during pregnancy.
In the final month of gestation, the concentration of progesterone begins to decline, increasing the excitability of the muscle.
What physiological changes occur in a patient in the early stages of acromegaly in regards to:
- Somatomedin C production
- Somatostatin secretion
- Insulin secretion
Excess GH (usually associated w/ pituitary tumor) –> acromegaly
Excess GH –> stimulates liver and other tissues to produce somatomedin C –> feedback causes hypothalamus to increase secretion of GHIH: somatostatin
Excess GH –> increase plasma glucose –> inc. insulin secretion
Which of the following findings would likely be reported in a patient with a deficiency in iodine intake?
a. weight loss
b. nervousness
c. increased sweating
d. increased synthesis of thyroglobulin
e. tachycardia
d. increased synthesis of thyroglobulin
b/c iodine is needed to synthesize TH, the production of TH is impaired if iodine is deficient. As a result of feedback, plasma levels of TSH increase and stimulate follicular cells to increase the synthesis of thyroglobulin –> this results in a goiter
A 30-year-old woman is administered cortisone for the treatment of an autoimmune disease. Which of the following is most likely to occur?
a. increased ACTH secretion
b. increased cortisol secretion
c. increased insulin secretion
d. increased muscle mass
e. hypoglycemia between meals
c. increased insulin secretion
Steroids with potent glucocorticoid activity tend to increase plasma glucose concentration. As a result, insulin secretion is stimulated.
Inc. glucocorticoid activity also diminishes muscle protein. Because of feedback, cortisone administration leads to a decrease in ACTH secretion and therefore, a decrease in plasma cortisol concentration.
Describe how hypothalamic factors regulate GH cells and affect bone, muscle, and fat.
Hypoglycemia, arginine, ghrelin, dopamine, serotonin, exercise –> GHRH (hypothalamus) –> GH release (from acidophils in AP) –> IGF (somatomedin-C) production by hepatocytes/ GH + GHBP and IGF-I + IGFBP –> target tissues
Somatomedin production triggers somatostatin production (GHIH) which exerts negative feedback on GH. Hyperglycemia also exerts negative feedback on GH.
Somatomedin also directly inhibits GH release.
Bone: growth/deposition
Muscle: Prevents glycolysis so that you have stores for contraction/prevents proteolysis/prevents glucose uptake
Fat: Stimulates beta oxidation of FFA (so that muscles can use this for direct fuel)
What are potential causes of hypothyroidism?
- Iodine deficiency: Lower TH –> rise in TSH –> hypertrophy of follicular cells to make more TH –> goiter (note: usually enough thyroxine made to avoid hypothyroidism)
- Iodine uptake or oxidation is impaired
- Autoimmune destruction of Tg or thyroid peroxidase (Hashimoto’s syndrome)
Propylthiouracil and mercaptoimidazole?
Antithyroid drugs (used for hyperthyroidism):
Blocks iodination of Tg by antagonizing thyroid peroxidase –> reduced production of T3 and T4
CV consequence of acromegaly: hypertension
GH excess has two main effects: H2O retention and vasoconstriction
- Hang onto too much water + activates aldosterone secretion (double whammy)
- VSM remodeling –> vasoconstriction stimulated
Ways to treat acromegaly
- Somatostatin analogues: octreotide, lanreotide
- GH-R antagonist on target tissues: Pegvisomant (so GH is still being made but target tissues can’t respond to it)
- Dopamine receptor agonists (Bromocryptine, cabergoline) b/c GH + PRL secretion is usually coupled
Physiological Actions of TH (6)
- Elevate BMR
- Inc. CO
- Inc. metabolic turnover
- Inc. body T
- Linear Growth (infants and children)
- Maturation of the CNS (perinatal period)
Cortisol and GH are most dissimilar in their metabolic effects on which of the following?
a. protein synthesis in muscle
b. glucose uptake in peripheral tissues
c. plasma glucose concentration
d. mobilization of triglycerides
a. protein synthesis in muscle
GH and cortisol have opposite effects on protein synthesis in muscle (GH = anabolic, cortisol = catabolic)
Both hormones impair glucose uptake in peripheral tissues
Both mobilize triglycerides from fat stores
Two days before the onset of menstruation, secretions of FSH and LH reach their lowest levels. What is the cause of this low level of secretion?
Estrogen and, to a lesser extent, progesterone secreted by CL during luteal phase have strong feedback effects on AP to maintain low secretory rates of both FSH and LH.
In addition, CL secretes inhibition, which inhibits the secretion of FSH.
When compared with the late-evening values typically observed in normal subjects, plasma levels of both ACTH and cortisol would be expected to be higher in which of the following individuals?
a. normal subjects after waking in the morning
b. normal subjects administered dexamethasone
c. patients with cushing’s syndrome (adrenal adenoma)
d. patients with addison’s disease
e. patients with conn’s syndrome
a. normal subjects after waking in the morning
Note: patients with cushing’s syndrome (adrenal adenoma); in these patients or in patients administered dexamethasone, plasma levels of ACTH are very low
In patient’s with conn’s: normal levels of ACTH and cortisol
During the latter stages of pregnancy, many women experience an increase in body hair growth in a masculine pattern. What is the explanation for this?
The maternal and fetal adrenal glands secrete large amounts of androgenic steroids that are used by the placenta to form estrogen.
A patient has hypothyroidism due to a primary abnormality in the thyroid gland. Increased plasma levels of which of the following would most likely be reported?
a. cholesterol
b. TBG
c. RT3
d. diiodotyrosine
e. iodide
cholesterol
Connection b/w adrenal medulla & cortex: The enzymatic conversion of norepi to epi is positively regulated by which steroid hormone?
cortisol
The metabolic actions of hormonal catecholamines (norepi and epi) are mediated via ____ and ____ adrenergic receptors.
Both _______ glucose production in the liver.
Epi acts more where?
Norepi acts more where?
Net effect of both?
alpha and beta
inc.
Epi = CV to increase HR and contractility
Norepi = selectively induce splanchnic, renal, cutaneous, and genital arteriolar vasoconstriction
To generate E and to shunt blood to critical organs and muscles essential for flight or fight response
Explain the biosynthesis of catecholamines in the adrenal medulla
Tyrosine –> DOPA –> Dopamine –> Norepi –> Epi
SNS stimulates tyr –> DOPA and chromaffin granules to release norepi and epi into the blood stream
Cortisol stimulates conversion of norepi into epi
20,22-desmolase (P-450scc)
Pregnenolone is transported out of the ___________ into the ________ where it becomes a substrate for alternative biosynthetic pathways to yield the three major classes of adrenocortical steroids: ______, ______, ______
20,22-desmolase (P-450scc): cholesterol –> pregnenolone
mitochon; ER; mineral… gluco… androgenic precursors
ZG lacks which enzyme complex?
What enzyme does it exclusively express?
CYP17 (17 lapha-hydroxylase/17,20-lyase)
aldosterone synthase
