Flashcards in "Medical Physiology Adrenal Gland Huaiyu Hu" 3/20 Deck (29):
The adrenal cortex is derived from what embryologic tissue?
The adrenal cortex is derived from mesoderm.
The adrenal medulla is derived from neural crest cells.
T/F: The total loss of the adrenal cortex is fatal within 4-14 days, whereas the total loss of the adrenal medulla is not.
What is the common precursor of adrenal cortical hormones?
What is the rate-limiting step in adrenal cortical hormone pathways?
The rate limiting step to forming androgens, testosterone (not part of adrenal repertoire), cortisol and aldosterone is a shared step from cholesterol --> pregnenolone
This step occurs in the mitochondria, and is catalyzed by 20,22 desmolase, aka "side chain cleavage enzyme"
What family do most adrenal cortical hormone-synthesizing enzymes belong to?
Except for cytosolic 3-beta-hydroxysteroid dehydrogenase, all enzymes belong to the cytochrome P-450 oxidase family.
Why is the rate of secretion of aldosterone by the adrenal gland limited by the rate at which the glomerulosa cells can synthesize the hormone?
Because there is no amount of preformed aldosterone ready for secretion
Why does the glomerulosa layer lack the ability to synthesize cortisol or androgens, even though all synthesis pathways of adreno-corticohormones are related?
The zona glomerulose lacks the enzyme to make androgens/cortisol, which is 17-alpha-hydroxylase.
What is the function of aldosterone?
The main action of aldosterone is stimulating the kidney (distal tubule) to increase Na (Cl) absorption. It does this by increasing protein transcription to put in more apical Na channels, and Na/K pump. A side effect of this is K secretion.
Aldosterone has similar effects in the colon, salivary and sweat glands.
Cortisol inhibits transcription of what gene?
How is cortisol transported in the plasma?
90% of cortisol is bound to CBP (cortisol binding protein or transcortin)
7% is bound to albumin
3% is free, and it is this cortisol that can diffuse into a cell and affect transcription.
What is the precursor to testosterone that is made in the adrenal cortex (zona fasciculata and reticularis)?
Androstenedione, which is converted to testosterone in peripheral tissues such as skin and fat.
DHEA is also a precursor to testosterone, but not directly. It has a peak in 20's and declines throughout life. It is thought to be important in maintenance of sex drive in postmenopausal females.
What are the two negative feedback targets of cortisol?
1. In the AP, cortisol inhibits expression of POMC gene and inhibits release of premade ACTH.
2. In the hypothalamus, cortisol decreases mRNA and peptide levels of CRH and inhibits release of premade CRH.
What are the major metabolic effects of cortisol?
1. stimulates gluconeogenesis in the liver
2. Enhances protein breakdown in muscle cells to provide aa's for gluconeogenesis
3. Stimulates lipolysis in adipose tissue
4. Decreases osteoblastic activity in trabecular bone
5. Interferes with Ca absorption in gut
What are the major anti-inflammatory effects of cortisol?
1. Inhibits cytokine production (inhibits cyclooxygenase activity and histamine release)
2. Inhibits production of chemo-attractant molecules
3. Stabilizes lysosomal enzymes
4. Contributes to vasoconstriction and decreased capillary permeability
Also, in the are of immunosuppression, cortisol:
1. decreases lymphocyte proliferation
2. inhibits hypersensitivity reactions, esp cell-mediated ones
T/F: Cortisol blocks glucose uptake except in the brain.
True. The brain has a diff glucose transporter than cortisol has no effect on.
What is the most potent mineralcorticoid?
What is the most potent exogenous glucocorticoid?
T/F: Cortisol is an equal mineralcorticoid and glucocorticoid.
What kind of receptor does ACTH use in the adrenal cortex?
ACTH stimulates all kinds of enzyme synthesis and is also a trophic factor for adrenal cortex survival (is needed for cortex cells to proliferate). Notably, ACTH increases P450 activity and stimulates the rate limited step in cortisol synthesis.
What is the difference between ACTH and cortisol?
ACTH is a peptide, whereas cortisol is a steroid.
CRH causes secretion of ACTH by the AP (GPCR pathway), and ACTH acts on the adrenal cortex to stimulate cortisol synthesis (cholesterol --> pregenolone).
Why does excessive licorice intake cause hypertension and kypokalemia?
Licorice contains "Glycyrrhetic acid," an inhibitor of 11-beta-hydroxysteroid dehydrogenase type II.
This enzyme typically converts cortisol to cortisone in the kidney.
Cortisol, but not cortisone, can bind with equal affinity to aldosterone receptors as aldosterone. If there is too much cortisol, there is falsely high aldosterone activity, wasting of K and too much retention of salt and water.
What is POMC?
POMC, pro-opiomelanocortin, is a pre-peptide that ca form many different peptide hormones in the corticotrophs of the AP. Notably, POMC becomes ACTH and beta-lipotropin.
During fetal development, POMC becomes alpha MSH and beta-endorphin.
When is cortisol highest in the blood, and what effect does this have?
Cortisol is highest in the blood in the early morning, owing to the diurnal variation of cortisol release. Cortisol stimulates gluconeogenesis which is why many people feel more alert in the morning (more brain food). Cortisol also increases appetite by inhibiting the anorexigenic center in the brain and stimulating nueropeptide Y.
Rhythmic secretion of ACTH influences cortisol production.
What is the effect of hypoglycemia on cortisol?
Stresses, including hypoglycemia, influence CRH secretion, enhanced ACTH secretion and cortisol synthesis. The result is increased blood glucose levels.
What is the effect of 21-alpha-hydroxylase deficiency?
21-alpha-hydroxylase deficiency, also called congenital adrenal hyperplasia, is a genetic mutation that causes decreased production of cortisol and aldosterone.
As a result, ACTH is increased, and causes adrenal hyperplasia, and these hormone precursors are instead shunted to produce androgens, which causes ambiguous genitalia in females. Other symptoms include hypotension due to salt loss, hypoglycemia and dehydration.
Prednisone can be used as a cortisol substitute to reduce ACTH levels.
How would you treat 17-alpha-hydroxylase deficiency?
17-alpha-hydroxylase deficiency is a genetic mutation that causes decreased production of cortisol and androgen synthesis bc this enzyme is common to all pathways but aldosterone.
Symptoms include increased ACTH, adrenal hyperplasia, hypokalemia and hypertension (because hormone precursors are shunted to aldosterone), pseudohermaphrodism/sexual infantilism in males.
Treatment includes glucocorticoidreplacement, plus estrogen for females. Males also benefit from testosterone and possibly surgery
What is the difference between Cushing's syndrome and Cushing's disease?
Cushing' syndrome is any etiology that causes hypercortisolism or hyperadrenocorticism. Symptoms include change in body fat distrbution, weight gain, osteopenia, muscle wasting and weakness, Skin thinning, glucose intolerance, hypokalemia and hypertension, increased length/severity of infections.
Cushing's Disease is an ACTH producing tumor or adrenal adenoma. Treat with surgery and prednisolone
Can dexamethasone feedback to inhibit cortisol synthesis?
Yes, bc it is an analog.
This is the dexamethasone suppresion test, which can distinguish between Cushing's syndrome and Cushing's disease. If dexamethasone is admin to a Cushing's syndrome patient, their cortisol remains high, but ACTH will drop due to feedback inhibition.