Endocrine Questions/Exercises and Notes
1. List a) most common steroid hormones, b) where their receptors are located, c) when they are
synthesized, and d) which one is the only one not attached to a protein carrier.
a. Steroid Hormones (are lipid soluble): Glucocorticoids, Mineralocorticoids, Androgens,
Estrogens, Progestagens, and Vitamin D (close relative b/c of sterol component)
b. Receptors are located Intracellular, usually in the nucleus
c. Synthesized as needed, not pre-formed (cannot be preformed if you are lipid-soluble,
since you’d cross the membrane of a pre-formed vesicle)
d. All attached to protein carrier except Adrenal Androgens
2. List a) lipid soluble hormones, b) half-life is proportional to, c) which one has longest half-life, d)
which ones can be measured in urine as diagnostic tests, and e) which lipid soluble hormone is
the only one that is stored (and it’s not stored in a vesicle, but covalently-bound)?
a. Steroid hormones, Vitamin D, Thyroid hormones
b. Half-life is directly proportional to the affinity of the hormone for its protein carrier
c. Longest half-life is T4 b/c its affinity is very high (99% of it is bound, too)
d. The ones that can be measured in urine, especially if being overproduced, are steroid
hormones with large percentages that are NOT bound to protein carriers, but free in the
blood. As you’ll learn in renal, substances bound to protein carriers cannot be filtered
b/c either they are too large or carry a negative charge (unless there is basement
membrane damage in the glomeruli, causing proteins to spill in urine). So, the steroid
hormone with the largest percentage unbound is cortisol, one of the glucocorticoids.
You’ll occasionally see mentioned a urine test called the 24-hour urinary free cortisol.
This test is used for diagnosing either underproduction of cortisol (Addison’s) or
overproduction (Cushing’s). Remember, the active form of hormone is the free portion,
so this test produces an accurate picture of the activity in the blood of cortisol.
e. Thyroid hormone is stored covalently-bound
3. List a) water-soluble hormones (proteins and peptides), b) location of their receptors, c) what
they activate to do their job, d) storage form, e) form of transport in blood, and f) half-life
determinant
a. Some examples are Insulin and Glucagon
b. Receptors are on cell surface (like Insulin’s Tyrosine Kinase receptor and Glucagon’s G
protein-coupled receptor / 7-transmembrane spanning receptor)
c. Act through second messengers, like Glucagon with cAMP and Insulin through the
tyrosine kinase receptor that autophosphorylates…they start cascades that activate
and/or deactivate many other substances.
d. Storage form is pre-formed stored in vesicles ready to be exocytosed. Insulin is stored
as a prohormone with an enzyme to cleave it to activate it once it’s needed. Once it’s
cleaved, C-peptide is released in an equal amount as Insulin.
e. Free, unbound dissolved in plasma is the transport form
f.
Short half-lives that are proportional to molecular weight
4. The free form (unbound) of lipid-soluble hormones is associated with all of the following except:
a. Active/available for tissues
b. Determines plasma activity
c. Is not filtered through glomeruli
d. Creates negative feedback
Answer: c, the free unbound form is the portion that is filterable through the kidney’s
glomeruli
5.
Because the free form of lipid soluble hormones is the portion that creates negative feedback, it
is the form that is precisely regulated. Which organ/organ system produces more binding
protein to carry the lipid-soluble hormones if it is stimulated to or it is necessary to produce
them?
a. Liver
b. Kidney
c. Skeletal Muscle
d. Small Intestine
e. Heart
Answer: a, liver. One very common way to stimulate the production of excess binding
proteins is through Estrogen. Estrogen – whether exogenous like Hormone Replacement
Therapy or high amounts during pregnancy/endogenous – stimulates the liver to produce
not only binding proteins, but clotting factors, and other proteins produced in the liver.
6.
In accordance with question #5, we know that because lipid-soluble hormones have a bound
fraction (bound to protein carriers). Since the liver produces these protein carriers, we can also
conclude that the bound fraction (and thus the unbound fraction) varies with liver function, or
the plasma concentration of protein. So, in cirrhosis, would you expect the bound fraction of
hormone to be lower or higher? Lower. But remember, because the bound fraction would be
lower, the free portion would be higher, thus creating negative feedback and stabilizing the
amount of active hormone in the blood (but decreasing the total amount of hormone).
7. So, in summary, the two things decreasing the circulating level of binding proteins are liver
dysfunction and androgens (testosterone), and the main substance increasing the level of
binding proteins is estrogen. But, remember, for example, that with Estrogen the transient
decrease in free hormone takes away negative feedback and stimulates the production of more
hormone and thus restoration of free hormones back to normal level…but there will be a slight
increase in the level of total hormone. So, slightly increased total thyroid hormone, for instance,
during pregnancy, is nothing to worry about b/c the free fraction remains the same (the active
form).
8. While ACTH only affects cells with receptors for it (adrenal cortex zona fasiculata/reticulate) and
LH only affects/stimulates gonadal tissue, both increase secretion of steroid hormones. ACTH
adrenal androgens and LH ovarian or testicular sex hormones.
9. We already mentioned that the free hormone level is what dictates hormonal activity. There
are some exceptions. For example, there are some conditions in which the number of
functioning receptors or post-receptor mechanism function will dictate hormonal activity:
a. Type II Diabetes Mellitus: the chronic high circulating levels of insulin downregulate the
receptors…so, you have a high circulating/free level of insulin, but its activity does not
match! There is insulin resistance.
b. Also, with SIADH, we have high ADH, but we may not form a concentrated urine, as is
expected, due to downregulation of receptors, once again…this would only happen after
a long time.
10. All hormones of the Hypothalamus-Anterior Pituitary System are: water soluble, synthesized in
the cell body of the neuron, and packed in vesicles and released from nerve terminals.
11. The only hypothalamic-anterior pituitary system hormone not synthesized in the arcuate or
paraventricular nuclei is: GnRH in the preoptic nucleus.
12. The name of where all nerve endings of hypothalamus come together to secrete hormones into
the anterior pituitary is: median eminence.
13. The two hypothalamic hormones that inhibit anterior-pituitary system hormones:
GHIH/Somatostatin inhibits GH and Prolactin Inhibiting Factor/Dopamine inhibits Prolactin.
14. The only hormone that will increase its secretion from the anterior pituitary if the pituitary stalk
(connection between hypoth and anterior pituitary) is damaged (Sheehan’s syndrome, head
trauma) is: Prolactin. You may think, why wouldn’t growth hormone also increase if GHIH is
decreased, or goes away…well, the truth is that growth hormone would decrease b/c the MAIN
factor regulating growth hormone is GHRH, not GHIH.
15. All hormone release from hypothalamic-anterior pituitary system is pulsatile except: Thyroid
Hormone system. This prevents downregulation of the sensitive anterior pituitary receptors.
For instance, if GnRH were constant, the target receptors on anterior pituitary for GnRH would
stop responding to GnRh after about a week, and therefore, stop releasing LH and FSH.
16. ACTH controls and regulates all adrenal cortex hormones except: Aldosterone (which is
regulated mainly and directly by Angiotensin II and is regulated slightly by high potassium
concentration and is regulated indirectly by Renin levels, since Angiotensin II levels directly
correlate with Renin levels.
17. Why do we see amenorrhea in women and decreased libido and impotence in men with
hyperprolactinemia? Because Prolactin suppresses the normal pulsatile pattern of GnRH and
therefore prevents the positive feedback effects of Estrogen on the gonadal tissue that creates
the LH surge necessary for ovulation; and LH drives testosterone secretion by the testes…if the
GnRH receptors of the anterior pituitary are downregulated, then, we’ll have no LH to drive this
testosterone secretion. Lab values in this hyperprolactinemia usually show decreased estradiol
and testosterone (b/c of no LH or FSH)
18. If we have an increased LH but a decreased testosterone, where is the problem? At the level of
the testis (you could say, a primary problem), b/c circulating testosterone provides negative
feedback to hypothalamus and anterior pituitary to regulate LH secretion.
19. Since LH drives the secretion of testosterone by the Leydig cells, can you think of a time(s) that
LH may need to be high? Fetus, where LH stimulates Wolffian duct development and the
development of the prostate and other external structures via DHT. And, during puberty, when
we re-stimulate the Leydig cells in preparation for reproduction.
20. The enzyme converting testosterone to DHT: 5 alpha reductase (peripherally-converts
testosterone to DHT)
21. While there are many hormones controlled by ACTH and released from the cortex, the ONLY
thing providing negative feedback on ACTH is Cortisol!
22. Along the same lines as question #21, if the anterior pituitary stalk gets damaged, what system
will not be affected (from the lack of ACTH)? The mineralocorticoid system, that responds to
Angiotensin II.
23. A board question: will you show signs of loss of regional adrenal function with a kidney
donation? NO, b/c a patient must have 80-90% loss of adrenal glands before he/she even starts
to show symptoms.
24. Absence of mineralocorticoids leads to: decreased ECF/decreased cardiac output, low BP,
possible circulatory shock and possible death (pharm treatment is fludrocortisone)
25. Absence of glucocorticoids leads to: possible circulatory failure b/c without cortisol, we lose the
permissive effect on catecholamines to exert their normal vasoconstrictive action in stressful
situations or with normal BP or blood volume fluctuations, and we also lose the ability to readily
mobilize glucose and free fatty acids, since cortisol also exerts permissive action on Glucagon
and catecholamines during stressful (metabolically-stressful) situations, like fasting and exercise.
26. The rate-controlling enzyme/step in adrenal cortex hormone synthesis is: Cholesterol to
Pregnenolone through Desmolase.
27. 21 Carbon substances are Aldosterone, Cortisol; 19 Carbons are Androgens (DHEA and
Testosterone) and 18 Carbons are Estradiol (through Aromatase conversion of Testosterone)
28. If a woman has hirsutism, it may be a result of excess androgens at the adrenal OR the ovary
level. Elevation of which form of DHEA says it’s an adrenal excess? DHEA-Sulfate (the sulfated
form), and this would be the form elevated, for instance, in a 21-Beta OH Deficiency (CAH)
29. 21 Carbon Steroid with an OH at position 17 is Cortisol … so, if you see “Elevated 17 OH
(hydroxy) steroids in the urine,” think cortisol excess.
30. Although DHEA is the major androgen secreted by the adrenal cortex, it’s very weak. So, it only
masculinizes in females when in excessive amounts, and it only masculinizes (precocious
puberty) in males with they are prepubertal!
31. All androgens, testicular and adrenal, are 17-KetoSteroids (19 carbon steroids with Ketone
group on position 17) because whenever testosterone is metabolized to its lipid-soluble form,
it’s converted to a 17-ketosteroid. So, urinary 17-ketosteroids are an index of both testicular
and adrenal androgens
32. When may urinary 17-ketosteroid only be an index of adrenal androgens? Female and prepubertal males
33. A normal ACTH/anterior pituitary response to low-dose dexamethasone is: suppresses ACTH and
therefore decreases cortisol.
34. The levels of renin and AGII in CAH (21-beta OH deficiency) are VERY HIGH, b/c lack of negative
feedback from aldosterone.
35. The only difference in 21-Beta OH def and 11-Beta OH def is that in 11-Beta OH deficiency, we
have hypertension b/c of 11-DOC having mineralocorticoid effects…just so happens, this
increased blood pressure inhibits renin and thus renin and AGII levels are LOW. 11-DOC
released in excess amounts b/c its synthesis and release is controlled by ACTH on the zona
fasiculata.
36. Interesting pharm/concept question: When would an AGII block (ACE inhibitor, AGII receptor
blocker) be insignificant in decreasing blood pressure? In 11-Beta OH deficiency, because the BP
increase comes from 11-DOC release from the zona fasiculata, not from aldosterone released
from zona glomerulosa…ACTH drives the 11-DOC. Even if Angiotensin II is working or available,
the enzyme necessary to make aldosterone is absent!
37. Elevated levels of growth hormone, glucagon in starvation…what stress hormone is not elevated
in starvation? Cortisol.
38. Cortisol raises blood sugar by 1) decreasing peripheral uptake in most tissues (anti-insulin effect)
in periphery and 2) by increasing gluconeogenesis (does not stimulate glycogenolysis; it’s just
permissive on glucagon)
39. Corticotrophs synthsize and release the stored form of ACTH that is Pro-opimelanocortin
(POMC), which makes ACTH, and B-lipotropin that makes Beta-MSH and Endorphins.
40. Aldosterone increases Na+ Reabsorption and K+ secretion in the principal cells of the collecting
duct, while increasing H+ secretion in the intercalated cells of the collecting duct.
41. Two direct actions of aldosterone on the principal cells of the collecting duct are: increased
activity of the Na/K ATPase pump (active Na+ reabsorption) and it also puts more Na+ channels
in the luminal membrane, to help with passive reabsorption of sodium.
42. Aldosterone tends to produce a metabolic alkalosis b/c it increases H+ secretion, drawn by the
increasingly negative luminal charge from increased Na reabsorption. For every H+ secreted,
one HCO3 is reabsorbed, so it also creates it this way… In a chronic state of metabolic alkalosis,
H+ ions leave the cell to buffer the alkalosis. K+ enters the cell, but with aldosterone it’s low
anyway…so we have a hypokalemic metabolic alkalosis.
43. Major difference between chronic and acute acidosis is that at first we have a positive K+
balance, but as acidosis continues, H+ ions enter the cell and K+ exits the cell to buffer the loss
of positive ions. Chronic acidosis produces a negative K+ balance.
44. Main cells regulating RAAS are modified smooth muscle cells surrounding afferent arteriole
called: Juxtoglomerular cells (Beta 1 receptors)…the macula densa of the distal tubule also
senses Na+ delivery and communicates with the JG cells.
45. Main thing stimulating renin release from JG cells is decrease in blood/perfusing pressure, but
an increase in SANS and decreased NaCl to macula densa also stimulate.
46. Causes of secondary hyperaldosteronism are: CFH, vena cava constriction, Hepatic cirrhosis
(fluid goes into intersitium from plasma), renal artery stenosis
a. Lab values are: renin and AGII levels are INCREASED, which drives the secondary
hyperaldosteronism (versus primary, which the levels are decreased); renin and AGII
levels are increased due to decreased CO and BP sensed by afferent arteriole JG cells
47. In islets of langerhans, delta and alpha cells are near periphery, while beta cells are near
center…blood enters centrally and goes peripherally, so glucagon cannot act locally on insulin,
but insulin can act locally on glucagon.
48. C-peptide is a better marker for endogenous insulin production than insulin itself, b/c all Cpeptide is delivered to the peripheral circulation – none is delivered to and removed by the liver,
like insulin.
49. Adipose tissue and resting skeletal muscle require insulin to uptake glucose through GLUT 4
transporters; Insulin accelerates but is not required by liver for glucose uptake; CNS tissue does
not require insulin for glucose uptake, nor do red blood cells, Beta cells of pancreas, kidney PT
or intestinal mucsosa (both of which uptake glucose through secondary active transport coupled
to sodium).
50. Insulin accelerates glucose uptake by the liver not by inserting transporters but by enhancing
glucose metabolism (PFK-2, which forms fructose 2, 6 bisphosphate, which stimulates PFK-1, the
rate-limiting step enzyme of glycolysis).
51. Anabolic hormones include: insulin, GH/IGF-1, Thyroid (euthyroid only**), and sex steroids
(androgens). Because they are anabolic, they conserve proteins and do not increase their
excretion, thus promoting a positive nitrogen balance.
52. Insulin promotes glycogen synthesis through stimulating glucokinase in liver and hexokinase in
muscle and glycogen synthetase. It also decreases glycogen phosphorylase and glucose-6phosphatase (liver only)
53. Insulin stimulates TG uptake by stimulating LPL in endothelial cells of capillaries, which clears
VLDL and chylomicrons from blood, and it stimulates TG synthesis by stimulating the ratelimiting step: carboxylation of acetyl CoA to malonyl CoA.
54. HSL breaks down TG into free fatty acids and glycerol; insulin inhibits HSL.
55. What can be used/given as an acute/fast K+ regulator, by stimulating the Na/K ATPase pump to
take up K+? Insulin. In hyperkalemia of renal failure, insulin and glucose may be given!