Lecture 31-Adrenal Steroids

Question 1

Esterase does what and is activated by what?

Answer 1

• cleaves cholesterol from the ester before its transported to the mitochondria
• activated by Angiotensin II, LH, and ACTH

Question 2

Which mutation leads to Congenital Lipid Adrenal Hyperplasia?

Answer 2

StAR

Question 3

isocaproaldehyde

Answer 3

6 C compound released during pregnenolone synthesis, made in all human steroid synthesis

Question 4

aminoglutethimide

Answer 4

a fairly non-specific inhibitory of P450SCC. -Also inhibits aromatase,

• increases turnover of some steroids and
• is most effective in the adrenal

Question 5

What are the major controlling mechanisms for the zona fasciculata, zona reticularis, and zona glomerulus?

Answer 5

• zona fasciculata: ACTH (gcc production)
• zona reticularis: ACTH (androgen production)
• zona glomerulus: renin-angiotensin system (mcc production)

Question 6

Where does 17alpha Hydroxylase not exist?

Answer 6

zona glomerulosa

Question 7

What is the one enzyme of the steroid synthesis pathway that is not a P450 enzyme?

Answer 7

• 3 beta hydroxysteroid DH ∆5-∆4 Isomerase

Question 8

Renin synthesis is inhibited by? (2)

Answer 8

• high salt

- high bp

Question 9

What are the functions of ACE inhibitors? (2)

Answer 9

• prevent degradation of vasodilator bradykinin by ACE

- help control (lower) bp

Question 10

AII functions? (3)

Answer 10

• stimulates aldosterone synthesis
• stimulates cortisol synthesis!!!
• vasoconstrictive on zona glomerulosa

Question 11

ANP functions (3)

Answer 11

• made in right atrium in response to stretch
• downregulates renin and therefore aldosterone
• inhibits aldosterone synthesis in glomerulosa

Question 12

What is Aldosterone synthesis controlled and not controlled by?

Answer 12

• stimulated by AII
• stimulated to a lesser extent by [K]
• it is NOT regulated by [Na] or ACTH

Question 13

What is an ACE inhibitor?

Answer 13

ramipril, aka Altace

Question 14

Name deoxycorticosterone, corticosterone, cortisol and aldosterone in order of the longest half life and say which carrier they bind, how much is free (non-carrier bound)

Answer 14

• Cortisol: CBG and albumin, 8% (T1/2: 1.5-2 hrs)
• corticosterone: CBG, __% (T1/2: <15min)
• deoxycorticosterone: albumin and CBG, 4% (T1/2: __)

Question 15

What protects MCC sensitive tissues from GCC binding?

Answer 15

11 beta hydroxysteroid DH

Question 16

Which estrogen to menopausal women use and why?

Answer 16

Estrone: it uses the adrenal cortex pathway because the ovaries don’t work the same with age so estrone can be converted using 16 hydroxylase to estriol

Question 17

Addison’s disease-cause and results

Answer 17

destruction of the adrenals

• Low GCCs: stress insensitivity and heightened sensitivity to insulin
• High POMC/ACTH: skin pigmentation from ACTH (which contains alpha MSH)

Question 18

Secondary adrenal insufficiency

Answer 18

• ACTH deficiency

- same symptoms as Addison’s, but no skin pigmentation

Question 19

Conn’s syndrom/Primary aldosteronism

Answer 19

• Glomerulosa adenoma
• high MCCs
• low renin, AII
• hypertension, edema, alkylosis

Question 20

Secondary Aldosteronism

Answer 20

• renal artery stenosis
• perceived low perfusion pressure causes renin to be over-released
• hypertension, edema, alkylosis

Question 21

Cushings syndrome

Answer 21

• GCC excess by any means
• truncal and abdominal obesity from cortisol-inducing gluconeogenesis
• bone weakness
• skin thinning
• thin arms and legs
• if ACTH is produced then high androgens
• hypertension, edema, alkylosis

Question 22

Cushings disease

Answer 22

• ACTH-releasing pituitary tumor

- same symptoms as Cushing’s syndrome with high ACTH and androgens

Question 23

Congenital Adrenal Hyperplasia

Answer 23

• steroid synthesis enzyme deficiency (90% deficient in 21 alpha hydroxylase, most others in 11 beta hydroxylase)
• high ACTH leads to high androgen synthesis and therefore:
• increased body growth
• virilization
• ambiguous genitalia
• remember: ACTH stimulates the zona reticularis which compounds the androgens even further