Adrenal Gland B&B

Question 1

how does venous drainage differ between the left and right adrenal gland?

Answer 1

Left adrenal drains into renal vein, which drains into IVC after crossing over

Right adrenal drains right into IVC

Question 2

from what is the adrenal cortex vs medulla derived?

Answer 2

cortex - mesoderm

medulla - neural crest (under SNS control)

Question 3

what are the parts of the pituitary-adrenal axis?

Answer 3

1. hypothalamus secretes CRH (corticotropin releasing hormone) from the paraventricular nucleus (PVN)
2. anterior pituitary secretes ACTH (adrenocorticotropic hormone), which stimulate cAMP/PKA in adrenal gland
3. adrenal cortex secrets cortisol

Question 4

how does estrogen affect the levels of cortisol within the plasma?

Answer 4

estrogen increases levels of cortisol binding globulin (CBG), the carrier protein for a cortisol in the plasma

Question 5

explain why peripheral neutrophil count rises in patients with high cortisol

Answer 5

cortisol suppresses the immune system by blocking neutrophil migration - neutrophils are trapped in the tissues, and can’t migrate into the vasculature

(also sequesters lymphocytes in spleen/lymph nodes)

Question 6

cortisol inactivates this key inflammatory transcription factor - what is?

Answer 6

NK-kB: controls synthesis of inflammatory mediators such as COX-2, PLA2, lipoxygenase

Question 7

what is the effect of chronically elevated cortisol on muscle, skin, and bones?

Answer 7

muscle – atrophy

skin - blunted cell division, decreased collagen, inhibition of fibroblasts —> thin skin, easy bruising, striae (can see small veins under skin)

bones - inhibits osteoblasts —> osteopenia and osteoporosis

Question 8

how is cholesterol converted to aldosterone and what are they key enzymes (4)?

Answer 8

1. cholesterol —> pregnenolone
2. —> progesterone via 3-beta hydroxysteroid dehydrogenase
3. —> 11-deoxycorticosterone via 21-alpha hydroxylase
4. —> corticosterone via 11-beta hydroxylase
5. —> aldosterone via aldosterone synthase

[3 Boys (Beta) turned 21 And (Alpha) had 11 Beers (Beta) - now they are Adults (Aldosterone)]

Question 9

how does angiotensin II stimulate the production of aldosterone from the adrenal glands?

Answer 9

activate aldosterone synthase, which converts corticosterone to aldosterone in the zona glomerulosa

Question 10

how is cortisol synthesized in the zona fasciculata and what are the key enzymes (4)?

Answer 10

1. pregnenolone OR progesterone from the above zona glomerulosa are converted to 17-hydroxy-pregnenolone/progesterone via 17-alpha hydroxylase (CYP17)
   1b. 17-hydroxypregnenolone —> 17-hydroxyprogesterone via 3-beta hydroxysteroid dehydrogenase
2. —> 11-deoxycortisol via 21-alpha hyroxylase
3. —> cortisol via 11-beta hydroxylase

[17 Added (Alpha) to 3 is Below (beta) 21, Above (Alpha) 11 - math gives me stress like Cortisol]

Question 11

how does ACTH stimulate the adrenal cortex to synthesize cortisol?

Answer 11

ACTH activates desmolase, which converts cholesterol —> prognenolone (by cleaving a side chain), which is then funneled into the cortisol synthesis pathway in the zona fasciculata

Question 12

how are androgens synthesized in the zona reticularis and what key enzyme is required?

Answer 12

1. 17-hydroxypregnenolone OR 17-hydroxyprogesterone from the above zona fasciculata are converted to androstenedione
   1b. if starting with 17-hydroxypregnenolone, first converted to DHEA (dehydroepiandrosterone), then to androstenedione via 3-beta hydroxysteroid dehdyrogenase
2. androstenedione —> testosterone

[3 layers Below (below) the top of the cortex is where Testosterone is made]

Question 13

what kind of drug is ketoconazole and what is its effect on the adrenal cortex?

Answer 13

ketoconazole: antifungal, blocks ergosterol synthesis in fungi

potent inhibitor of 17,20 lyase, necessary for testosterone production —> gynecomastia

also inhibits 17-alpha hydroxylase (CYP17) and desmolase necessary for cortisol synthesis —> can be used to treat Cushing’s syndrome

[I went KETO at 17]

Question 14

how are the layers of the adrenal cortex ordered? what is produced in each?

Answer 14

1. zona glomerulosa (outermost) - mineralcorticoids
2. zona fasciculata - glucocorticoids
3. zona reticularis (innermost) - androgens

G-F-R

Question 15

which cells produce testosterone in males and females, respectively?

Answer 15

males - testicular Leydig cells

females - ovarian theca cells

Question 16

what has to happen to DHEAS (adrenal androgen) for it to be used as a precursor for bioactive androgens (testosterone and dihydrotestosterone) and estrogens (estradiol-17beta and estriol)?

Answer 16

must be desulfonated by steroid sulfatase - expressed within placenta, ovaries, testes

Question 17

what is the most common form of congenital adrenal hyperplasia (CAH)?

Answer 17

21 hydroxylase deficiency - required for production of both aldosterone and cortisol

loss of cortisol-dependent negative feedback of ACTH leads to unchecked ACTH secretion —> high steroidogenesis of DHEAS and androstenedione

Question 18

name a bioactive and weakly active example of each of the following families of steroids (in normal, non-pregnant individuals):
a. androgens
b. estrogens
c. glucocorticoids
d. mineralocorticoids
e. progestins

Answer 18

a. androgens: testosterone, DHT (strong) / androstenedione, DHEAS (weak)
b. estrogens: estradiol (strong) / estriol, estrone (weak)
c. glucocorticoids: cortisol (strong) / cortisone (weak)
d. mineralocorticoids: aldosterone (strong) / corticosterone (weak)
e. progestins: progesterone (strong) / pregnenolone (weak)

Question 19

what are the primary sources of estrogen in females vs males?

Answer 19

females: ovarian granulosa cells, corpus luteum, placenta

males: testicular Leydig cells

Question 20

the production of _______ from cholesterol marks the onset of de novo steroidogenesis

Answer 20

pregnenolone

Question 21

the adrenal zona fasciculata and zona reticularis cannot produce testosterone and DHT because they lack which 2 necessary enzymes?

Answer 21

1. 17-beta HSD (converts androstenedione to testosterone)
2. 5-alpha reductase (converts testosterone to DHT)