TF Binds to genes w/ GRE> can up and down regulate trxn

Rose: Adrenal and Pancreas Physiology Flashcards by Sarah Carlson

What are the 3 zones of the adrenal cortex and what do they do?

G= mineralcorticoids (aldosterone)
F= glucocorticoids (cortisol)
R= androgens

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What part of the adrenal gland is a modified sympathetic ganglion that DIRECTLY releases catecholamines?

Medulla

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Where is ACTH synthesized?

Corticotrophs

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What is the primary ACTH receptor? Where is it expressed?

MC2-R (Melanocrotin receptor)

Adrenal cortex

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Where is MC2-R also locate?

skin melanocytes and adipocytes (mediates stress induced lipolysis)

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ACTH binds MC2-R then what….

GaPCR>
increased cAMP>
signal transduction cascade

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How does ACTH affect CYP11A (side chain cleavage enzyme) synthesis in the adrenal cortex? Why?

PROMOTES synthesis

This rxn is REQUIRED for cholesterol conversion to pregnolone

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What is the RLS in adrenal steroid syntehsis?

CYP11A

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What is the primary active glucocorticoid and what does it do?

Cortisol>
binds glucocorticoid receptor>
increases glucose levles

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How does cortisol promote gluconeogenesis?

Cortisol>
mobilizes AA from proteins>
liver>
gluconeogenesis

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A def of cortisol may cause?

hypoglycemia

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What does aldosterone do?

Promotes Na and H20 retention

binds mineralcorticoid receptor (MR)

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What is the main sex steroid and what does it bind to?

DHEA, androstenedione and some testonsterone (minor site for estrogen synthesis)>
binds Androgen receptors

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What percent of cortisol is bound to a carrier protein?

90%

60%= CBG= transcortin
30%= albumin

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What leads to an increase in CBG?

estrogens

pregnancy

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What leads to a decrease in CBG?

increased cortisol and liver cirrhosis

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Where are GR located and what family do they belong to?

expressed in every cell in the CYTOPLASM

Nuclear receptor super family

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What happens when hormone binds the GR?

Hormone binds receptor>
translocation to the nucleus>
homodimer

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What is a homodimer?

Binds to genes w/ GRE>
can up and down regulate trxn

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What hormone has the highest affinity and potency for GR?

cortisol

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What is an example of a MR?

Aldosterone REceptor

NR3C2

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WHere are aldosterone receptors found?

kidney, colon, sweat glands, heart, hippocampus, brown adipose

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Which has greater effect in mineralcorticoid responsive tissues–cortisol or aldosterone?

Cortisol is converted to cortisone in MCR tissues which is metabollically inactive>
cortisone has NO effect and aldosterone can act

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What are the physiological effects of coritsol?

carb met> increased gluconeogenesis + decreased glucose uptake by muscle and fat> increased plasma glucose
fat met: increased lipolysis> increased free FA
Protein met: increased proteolysis> increased N excretion

What are the effects on the body of sustained cortisol levels?

``` reproductive capacity fat redistribution muscle atrophy collagen brkdown bone loss anti-inflammaotry ```

What are the physiological effects of mineralcorticoids (aldosterone)?

1. stimulates Kindey reabsorption of Na and water 2. stimulates N and water reabsorption in teh colon, salivary glands, sweat glands 3. enhances kidney K excretion

Hypersecretion of aldosterone can lead to...

HTN

What does the activity of glucocorticoid/steroid depend on?

tissue enzyme expression

What does 11BHSD2 do?

It OXIDIZES active steroid to inactive steroid

What tissues is 11BHSD2 active in?

Kidney, colon, SG, placenta, fetus | mineralcorticoid responsive tissues

What does 11GHSD1 do?

Reduces inactive steroid to ACTIVE steroid

Where is 11.BHSD1 active?

LIVER ADIPOSE | lung, vascular tissue, CNS

What does most glucocorticoid metabolism ocur?

liver cortisone and cortisol are rapidly conjugated> tetrahydrocortisone and tetrahydrocortisol glucuronide/sulfate

Are derivatives of glucocorticoid metabolism soluble in the serum?

YES and excreted by the kidneys

How do you assess adrenal steroid production?

24 hr urine collection

What are the main sources of cholesterol?

diet, liver, de novo synthesis

What regulates side chain cleavage of cholesterol?

ACTH *RATE LIMITING

What is prenenolone?

common precursor to mineralcorticoids, glucocorticoids and androgens

What step in adrenal steroidogenesis is common to all pathways?

cholesterol> progenolone

What happens to pregenolone in the aldosterone pathway?

progesterone> 11-deoxy-corticosterone> corticosterone> aldosterone

What happens to pregenolone in the cortisol pathway?

``` → 17α hydroxyl-pregnenolone → 17α hydroxyl-progesterone – (*21 hydroxylase) → 11-deoxycortisol – (*11b hydroxylase) → cortisol ```

What happens to pregenolone in the androgen pathway?

``` → 17α hydroxyl-pregnenolone → DHEA → Androestenediol OR → 17α hydroxyl-pregnenolone → 17α hydroxyl-progesterone → androstenodione → Testosterone ```

What is the rate limiting enzymes involved in side chain cleavage in steroid synthesis from cholesterol?

CYP11A1

What defect in steroid synthesis is responsible for 95% of genetic abnormalities and can lead to CAH?

CYP21A-21-hydroxylase

What is the second MC enzymatic defect that can also cause CAH?

CYP11B1

What is CYP11B2?

aldosterone synthase

What are the sxs of 21 hydroxylase def?

decreased cortisol AND aldosterone> virilization and HOTN (losing salt and reducing BV) Increased: ACTH, enzymes, androgens

What are the sxs of 11B-hydroxylase def?

Virilization (increased androgens) | HTN (increased deoxycorticosterone)

What has tonic control over mineralcorticoid regulation?

ACTH

What stimulates mineralcorticoid synthesis?

HIGH levels ACTHa nd normal level AT II>> increases/maintains BP

Does aldosterone NGB on ACTH?

What can cause Hypercortisolism?

1. Adrenal cortex: tumor/hyperplasia> excess cortisol production> cushing syndrome 2. Pituitary adenoma (MC), hypothalamic cuase 3. Taking steroids, morbid obesity, DM2> Cushing syndrome

What are the effects of hypercortisolism?

``` Moon face bufallo hump thin skin high BP red striae pendulous abdomen ```

How do you dx hypercortisolism?

Increased ACTH (pituitary adenoma) Increaed cortisol (iatrogenic, adrenal gland problem)

What causes hypocortisolism?

1. immune mediated destruction of adrenal cortex> addison disease 2. w/drawal of exog glucocorticoid> iatrogenic

What are the effects of hypocorisolism?

fatigue/weakness anorexia, wght loss diarrhea HYPERPIGMENTATION

What causes hyperpigmentation observed in Addisons?

increased POMC> increase in both ACTH and MSH> hyperpigmentation via MC-R

How do you dx Addisons?

decrease in cortisol and aldosterone