L7 - Adrenal Glands Flashcards by Zachary Stielper

What is the principal glucocorticoid in humans? Principal mineralocortiocoids?

Cortisol; Aldosterone

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What hormone categories are produced in the adrenal cortex hormones? In the medulla?

Glucocorticoids, mineralocorticoids, androgens; epinephrine and norepinephrine

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How does the hypothalamus regulate the production of adrenal cortex hormones?

Hypothalamus releases corticotropin releasing hormone which binds to corticotrophs of the anterior pituitary and stimulates release of adrenocorticotropic hormone

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How do predisone and dextramethosone affect the release of adrenal cortical hormones?

Inhibits release of CRH and ACTH

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What negative feedback mechanisms are involved in the regulation of adrenal cortical hormone production?

Cortisol inhibits the release of CRH and ACTH

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What is the effect of ACTH binding to its receptor in the adrenal cortex?

Activation of PKA, which activates cholesterol ester hydrolase and steroid acute regulatory protein (STAR)

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What biochemical step commits cholesterol to steroid hormone synthesis?

The conversion of cholesterol to pregnenolone

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Into what compounds can pregnenolone be converted?

Progesterone and 17- alpha hydroxy pregnenolone

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What hormones can be derived from progesterone?

Aldosterone and cortisol

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What hormones can be derived from 17-alpha-hydroxypregnenolone?

Cortisol, androstenedione, testosterone, estradiol,

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What is the half life of cortisol? How does it circulate in the blood?

70-90 min; circulates mostly bound to cortisol binding protein and albumin

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Into what compound is cortisol metabolized? Is it more or less active?

Cortisone– less active

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How is cortisol metabolized?

Tissue conversion to cortisone, biotransformation in the liver, urinary excretion

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How can an accurate cortisol level be obtained?

Urine levels over a 24 hr. period must be measured

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What is the main stimuli for adrenal release of aldosterone?

Angiotensin II binding to Angiotensin I GPCR; K+ stimulates calcium influx

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How does aldosterone circulate? What is its half life? Does it circulate at higher or lower levels than cortisol?

Free; 15-20 min; lower than cortisol

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How is aldosterone metabolized and excreted?

Phase I and II of biotransformation in the liver and is excreted through the urine in the forms of several metabolites

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What are the effects of glucocorticoid and mineralocorticoid binding to their receptors? Where in the cell is the receptor located?

Hormones bind to their cytosolic receptor, releasing regulatory proteins and exposing nuclear localization signals, which facilitates the translocation into the nuclues where it affects gene transcriptino by binding to hormone response elements in the DNA

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What are the two types cortical hormone receptors? To which compounds do they have affinity?

Type I mineralocorticoid receptor is specific for mineralocorticoid but also has a high affinity for glucocorticoids; Type II glucocorticoid receptors are specific for glucocorticoids.

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How is the binding of cortisol to mineralocorticoid regulated?

Cortisol can be converted to cortisone which will not bind to the MR receptor

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What determines the specificity of mineralocorticoid action?

Localization of the mineralocorticoid receptor (mostly kidney), , the presence of 11beta- hydroxysteroid dehydrogenase type II, and the greater affinity of MCR to aldosterone

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What are the effects of cortisol on metabolism?

Cortisol antagonizes insulin action by favoring an increase in gluconeogenesis and decrease in glucose utilization, decreases protein synthesis and increased proteolysis, increases FA mobilization and inceases central adiposity

How does cortisol affect the immune system?

Potent anti-inflammatory and immunosuppresant effects- suppresses the synthesis of pro-inflammatory cytokines

What are the overall physiologic effects of cortisol on the circulatory system?

Maintains vascular integrity and maintains responsiveness to vasoactive substances, contributes to sodium retention and affects body fluid volume

What is the principal physiologic function of aldosterone? What is the principal target?

To regulate mineral (sodium and potassium) balance; Kidney

How does aldosterone affect the principal cells of the kidney?

The main effects is to increase synthesis of sodium transporters into the apical membrane and increase their activity and increase expression of Na+/K+ ATPase in the basolateral membrane. The reabsorption of Na (and thusly water) into the cell stimulates the excretion of potassium into the lumen

How does alsosterone affect the intercalated cells of the kidney

Increase H+ excretion by activating H+ ATPase pump

How does a drop in blood volume/ pressure mediate and increase in aldosterone release? How does this aid in solving the problem?

The kidney will release renin which converts angiotensinogen to angiotensin I, which is converted to angiotensin II by angiotensin converting enzyme. Angiotensin is a potent vasoconstictor and will stimulate the release of aldosterone; Increasing sodium and water reabsorption will increase blood volume

What is the main adrenal androgen? Into what compounds can it be converted?

Dehydroepiandrosterone (DHEA); Into testosterone or estrone

True or False: Testosterone is produced in the adrenal cortex?

False

What are the main effects of androgens?

Masculinizing effects, contribute to libido, anabolic, less potent that testosterone

What occurs with excess production of adrenal androgens in adults? In prepubescent children? In females?

In adults viralization, in children- precocious development of secondary sex characteristics and growt;in females- pseudohermaphroditism and andrenogenital syndrome

Mutation in which enzyme is the most common cause of congenital adrenal hyperplasia?

21 hydroxylase

How would a deficiency in 21 hydroxylase present? What hormones are affected?

The conversion of progesterone to aldosterone and cortisol would be blocked resulting in increased formation of DHEA, causing masculinization, low cortisol and aldosterone levels, and loss of sodium

How would a deficiency in 11 beta hydroxylase present?

Excess 11-deoxycortisol and 11-deoxycorticosterone leading to excess mineralocorticoid activity-- sodium and water retention, and high blood pressure, masculinization

What is the difference in Cushing's Syndrome and Cushing's disease?

It is only called disease if there is a pituitary tumor

What condition results from an excess in cortisol? How does it manifest?

Cushing's; Truncal obesity, glucose intolerance, hypertension, edema, mood disorders, osteoporosis, gonadal dysfunction, fungal infections

What is Addison's disease? How does it manifest?

Adrenal insufficiency due to adrenal cortex destruction; Hypoglycemia, weight loss, vasodilation, hyponatremia, hypovolemia, fatigue, autoimmune disease, pigmentation

What is Conn's syndrome? Barter's syndrome?

Conn's is primary hyperalsosteronism due to adrenal tumors, Barter's is genetic tertiary hyperaldosteronism

What are the symptoms/signs of each type of hyperaldosteronism?

Primary- hypertension and hypokalemia; Secondary- decreased blood volume; tertiary- NaCl wasting

How do renin levels differ between primary and secondary hypoaldosteronism

Primary will have high renin, and secondary will have low renin since it is due to renal insufficiency

What hormones are synthesized by the adrenal medulla? What cells produce them?

Chromaffin cells (pheochromocytes) secrete norepinephrine, epinephrine and dopamine

What regulates the conversion of tyrosine to DOPA by tyrosine hydroxylase? What regulates conversion of norepinephrine to epinephrine?

Norepinephrine; cortisol

How is release from chromaffin cells triggered? What is the ratio of epinephrine to norepinephrine released

Sympathetic preganglionic neurons released ACh which binds and triggers release; 80% epi: 20% NE

What is the relative affinities for Epi and NE for the adrenergic receptors?

B1 receptors have approximately equal affinity, but all others have higher affinity for epinephrine

What are the effects of binding to alpha 1 receptors? alpha 2?

A1-VSM contraction, increased contractility, increased glycogenolysis, increased gluconeogenesis, and intestinal SM relaxation; A2- VSM contraction, decreased insulin release

What are the effects of binding to beta 1, beta 2,and beta 3 receptors?

B1- increased contractility, increased HR, increased renin release; B2- bronchodilation, intestinal smooth muscle relaxation, and increased glycogenolysis; B3- lipolysis

How are catecholamines metabolized?

Can be metabolized by monoamine oxidase or catechol-O-methyltransferase into metanephrine, normetanephrine and ultimately vanillylmandelic acid

(L7) Excess glucocorticoids (i.e., cortisol, prednison, dexamethason, etc) will a) delay resolution of inflammation b) increase susceptibility to infections c) increase resistance to viral infections d) none of the above

b) increase susceptibility to infections glucocorticoids decrease pro-inflammatory, decrease immune system

(L7) Glycyrrhic acid in licorice decreases 11beta-OH steroid dehydrogenase II activity, this can result in: a) virilzation b) increased risk for infections c) hypovolemia d) hypertension

d) hypertension 11beta-OH dehydrogenase II activity blocks the formation of cortisol, shunting the pathway to the production of androgens. increase in androgens => kidney retention => hypertension

(L7) One can predict that adults that live in Iceland, in comparison to NOLA residents, may a) have higher levels of 24,25-OH vitamin D b) have lower risk for osteoporotic fractures c) have increased 1-alpha hydroxylase activity d) have lower PTH levels

c) have increased 1-alpha hydroxylase activity colder residence: have no sunlight, little vitamin D; 1-alpha hydroxylase is the enzyme that catalyzes the formation of active vitamin d a - 24,25-OH vitamin D is inactive form b - should have higher risk because low calcium; don't see sun d - have high PTH due to it being released in response to low calcium levels

``` (L7) CLINICAL CASE 23yo male with history of -1y diabetes -hypertension -hypogonadism -weight gain of 22 kg ``` Physical exam: abdominal stria lab values AM cortisol post-Dex suppresion 38 ug/dl [<1.8 ug/dl] CRH 287 pg/ml [<46] This patient most likely has: a) pituitary tumor releasing excess ACTH b) hypothalamic tumor releasing excess CRH c) cogenital adrenal hyperplasia d) ectopic CRH producing tumor e) adrenal adenoma

d) ectopic CRH producing tumor cortisol levels did not change

(L7/8) Counteregulation to hypoglycemia involves: a) somatostatin-mediated increase in glucagon release b) GH-mediated inhibition of lipolysis c) glucagon-mediated stimulation of gluconeogenesis d) ephinephrine-mediated suppression of glycogenolysis e) glucagon-mediated increase in hepatic glycogen synthesis

c) glucagon-mediated stimulation of gluconeogenesis low glucose in blood, want to increase glucose in blood => release glucagon c - epinephrine (SNS) - during stress, would want to stimulate glycogenolysis (breakdown of glycogen to make energy) d - liver wants to breakdown glycogen in response to low glucose in blood