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U6 Physiology > Adrenal Gland - RM > Flashcards

Adrenal Gland - RM Flashcards

1
Q

What is adrenal cortex derived from?

A

mesoderm

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2
Q

What are the three layers of adrenal cortex and what do they secrete?

A

zona glomerulosa-mineralocorticoids
zona fasiculata- glucocorticoids, some androgens
zona reticularis- androgens, some glucocorticoids

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3
Q

What is the adrenal medulla derived from?

A

neural crest

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4
Q

What does adrenal medulla secrete?

A

norepinephrine, epinephrine, DOPA, dopamine

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5
Q

Is the adrenal cortex or adrenal medulla essential for life?

A

adrenal cortex

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6
Q

What is the common precursor of all adrenal cortical hormones? Where does it come from?

A

cholesterol, from LDL in blood or de novo synthesis

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7
Q

What is the rate limiting step in cortical hormone synthesis? What enzyme catalyzes it?

A

conversion of cholesterol to pregnenolone by P450 side chain cleavage enzyme/20,22-desmolase (same enzyme, different names)

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8
Q

What enzyme is not part of the cyt.P450 oxidase complex?

A

3 beta hydroxysteroid dehydrogenase

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9
Q

What does 3beta hydroxysteroid dehydrogenase catalyze?

A

conversion of prenenolone to progesterone

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10
Q

What does 21 alpha hydroxylase catalyze? Where does this occur?

A

conversion of progesterone to 11-deoxycorticosterone

-in SER

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11
Q

What does 11 beta hydroxylase catalyze? Where does this occur?

A

conversion of 11-deoxycorticosterone to corticosterone

-in mitochondria

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12
Q

What oxidizes corticosterone to aldosterone?

A

aldosterone synthase

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13
Q

What synthesizes cortisol?

A

17 alpha hydroxylase

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14
Q

Because of its lack of substrate specificity, what does 17 alpha hydroxylase act on?

A

-acts on corticosterone, pregnenolone, and progesterone

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15
Q

What does 17,20-desmolase do?

A

generates DHEA and androstenedione (androgens)

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16
Q

How are 17 alpha hydroxylase and 17,20 desmolase related?

A

same enzyme but two different catalytic sites

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17
Q

Why can’t adrenal cortex make testosterone?

A

there is no 17 ketyl reductase to convert androstendione to testosterone

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18
Q

How is testosterone produced outside of the testes?

A

peripheral tissue has small amounts of 17 ketyl reductase in adipose tissue that can act on androstendione

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19
Q

Why is aldosterone the only thing produced in zona glomerulosa?

A
  • no 17 alpha hydroxylase expression so can’t produce cortisol or androgens
  • has aldosterone synthase
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20
Q

What does aldosterone do?

A

increases transcription of Na/K pump and expression of apical Na channels to increase Na reabsorption and K secretion to reabsorb water

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21
Q

Why isn’t aldosterone produced in zona fasiculata or reticularis?

A

no aldosterone synthase

22
Q

How is cortisol transported in plasma?

A

90% bound to cortisol binding protein (CBP/transcortin)
7% bound to albumin
3% free

23
Q

What is DHEA associated with?

A

aging, highest in 20s and declines after

24
Q

How does cortisol effect its changes?

A

free cortisol enters target cell by diffusion, binds cytosolic receptor, causes it to dissociate from heat shock proteins, transports to the nucleus, binds hormone response, modulates transcription

25
Are steroid hormones stored?
No, once synthesized, they are secreted into blood
26
How is cortisol release regulated?
feedback inhibition by cortisol on CRH and ACTH - CRH release inhibited, decreased CRH mRNA and peptide levels - ACTH release inhibited and transcription of POMC gene inhibited (from which ACTh is formed)
27
What are the metabolic effects of cortisol?
- stimulates gluconeogenesis in liver - enhances protein breakdown in muscle to provide amino acids for gluconeogenesis - stimulates lipolysis as alternate fuel for glucose - decreases osteoblastic activity and interferes with Ca absorption from gut - inhibits glucose transporters to block glucose uptake (except in brain)
28
Why doesn't cortisol inhibit glucose uptake in brain?
glut3 receptor doesnt respond to cortisol
29
What are the antiinflammatory effects of cortisol?
- inhibits production of cytokines and chemoattractant molecules - stabilize lysosomal enzymes - contributes to vasoconstriction and decreased capillary permeability
30
What are the immunosuppressive effects of cortisol?
- decrease lymphocyte proliferation - inhibits hypersensitivity reactions (esp. cell mediated) - inhibits expression of interleukins (esp IL-2) and IL receptors and Fc receptors on macrophages
31
What cortisol analog has no mineralcorticoid activity? What is its glucocorticoid potency?
dexamethasone | 25-80x glucocorticoid potency
32
What is the intracellular signaling pathway of CRH? What does prolonged CRH exposure cause?
- binds GPCR CRH receptor to increase adenylyl cyclase, cAMP, PKA, intracellular calcium, and exocytosis of ACTH in vesicles - prolonged exposure causes ACTH synthesis in corticotrophs
33
What is the intracellular signaling pathway of ACTH?
- binds melanocortin 2 receptor, increases adenylyl cyclase, cAMP, PKA, P450 side chain cleavage enzyme/20,22 desmolase - activates and increases synthesis of cortisol
34
Why is ACTH the most important regulator of cortisol?
stimulates rate limiting step enzyme of cortisol synthesis
35
What acts as a trophic factor for adrenal cortex?
ACTH
36
What does the POMC gene code for in anterior pituitary?
ACTH, beta-lipotropin
37
What does POMC gene code for in intermediate pituitary lobe in fetuses and pregnancy?
alpha-MSH, beta-endorphin
38
Why does cortisol have diurnal (daily) variation?
info about light/dark cycle conveyed to hypothalamus which regulates pulsatile secretion of CRH and ACTH
39
When are levels of cortisol highest? What do peaks follow pulses of?
cortisol highest in the early morning, rhythmic secretion of ACTH before each peak
40
What is the most common form of congential adrenal hyperplasia?
21 alpha hydroxylase deficiency
41
What does 21 alpha hydroxylase deficiency present with?
Decreased cortisol -hypoglycemia, increase ACTh production-->adrenal hyperplasia (negative feed from cortisol is gone) Decreased aldosterone -loss of salt, hypotension, dehydration Increased androgen secretion -virilization in males, ambigious genitals in female
42
How is 21 alpha hydroxylase deficiency diagnosed?
elevation of 17 hydroxyprogesterone before and after ACTH stimulation
43
How is 21 alpha hydroxylase deficiency treated with hormone replacement therapy?
analogs of cortisol (prednisolone or dexamethasone) to reduce ACTH, adrenal hyperplasia and excess androgens -mineralcorticoids replaced by fludrocortisone
44
What does 17 alpha hydroxylase deficiency present with?
- reduced cortisol and androgen synthesis - increased aldosterone-->causes hypertension and hypokalemia - reduced estrogen synthesis - increased corticosterone (weak glucocorticoid), which mitigates adrenal insufficiency so no hypoglycemia
45
What is Cushing's syndrome?
hyperadrenal function -excessive levels of cortisol caused by prolonged immunosuppression drugs, adrenal tumors, ACTH secreting tumors, ectopic ACTH syndromes
46
What is Cushing's disease?
hypercortisolism secondary to ACTH excess from pituitary adenoma
47
What are the symptoms of Cushing's syndrome?
moon face, increased fat around neck, thinning of arms (change in body fat distribution), osteopenia, increased frequency and severity of infections, muscle wasting, hypokalemia, hypertension
48
How do you diagnose Cushing's disease?
- dexamethasone suppression test - analog of cortisol so should lower ACTH by feedback inhibition - won't see that in ACTH producing tumor though
49
What is Addison's disease?
hypoadrenal function - failure to produce enough cortisol-->hypoglycemia, weakness, weight loss, poor tolerance to stress - lack of aldosterone-->hypotension, hyperkalemia
50
How do you diagnose Addison's disease?
1. test cortisol levels 2. ACTH stimulation test--won't show increased cortisol 3. CRH stimulation--ACTh should increase but cortisol won't
51
How will primary and secondary adrenal insufficiency present differently in CRH stimulation test?
primary- high ACTH, low cortisol | secondary- low cortisol, but absent or delayed ACTH response

U6 Physiology (13 decks)

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