Lecture 31-Adrenal Steroids Flashcards
Esterase does what and is activated by what?
- cleaves cholesterol from the ester before its transported to the mitochondria
- activated by Angiotensin II, LH, and ACTH
Which mutation leads to Congenital Lipid Adrenal Hyperplasia?
StAR
isocaproaldehyde
6 C compound released during pregnenolone synthesis, made in all human steroid synthesis
aminoglutethimide
a fairly non-specific inhibitory of P450SCC. -Also inhibits aromatase,
- increases turnover of some steroids and
- is most effective in the adrenal
What are the major controlling mechanisms for the zona fasciculata, zona reticularis, and zona glomerulus?
- zona fasciculata: ACTH (gcc production)
- zona reticularis: ACTH (androgen production)
- zona glomerulus: renin-angiotensin system (mcc production)
Where does 17alpha Hydroxylase not exist?
zona glomerulosa
What is the one enzyme of the steroid synthesis pathway that is not a P450 enzyme?
- 3 beta hydroxysteroid DH ∆5-∆4 Isomerase
Renin synthesis is inhibited by? (2)
- high salt
- high bp
What are the functions of ACE inhibitors? (2)
- prevent degradation of vasodilator bradykinin by ACE
- help control (lower) bp
AII functions? (3)
- stimulates aldosterone synthesis
- stimulates cortisol synthesis!!!
- vasoconstrictive on zona glomerulosa
ANP functions (3)
- made in right atrium in response to stretch
- downregulates renin and therefore aldosterone
- inhibits aldosterone synthesis in glomerulosa
What is Aldosterone synthesis controlled and not controlled by?
- stimulated by AII
- stimulated to a lesser extent by [K]
- it is NOT regulated by [Na] or ACTH
What is an ACE inhibitor?
ramipril, aka Altace
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)
- Cortisol: CBG and albumin, 8% (T1/2: 1.5-2 hrs)
- corticosterone: CBG, __% (T1/2: <15min)
- deoxycorticosterone: albumin and CBG, 4% (T1/2: __)
What protects MCC sensitive tissues from GCC binding?
11 beta hydroxysteroid DH
Which estrogen to menopausal women use and why?
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
Addison’s disease-cause and results
destruction of the adrenals
- Low GCCs: stress insensitivity and heightened sensitivity to insulin
- High POMC/ACTH: skin pigmentation from ACTH (which contains alpha MSH)
Secondary adrenal insufficiency
- ACTH deficiency
- same symptoms as Addison’s, but no skin pigmentation
Conn’s syndrom/Primary aldosteronism
- Glomerulosa adenoma
- high MCCs
- low renin, AII
- hypertension, edema, alkylosis
Secondary Aldosteronism
- renal artery stenosis
- perceived low perfusion pressure causes renin to be over-released
- hypertension, edema, alkylosis
Cushings syndrome
- 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
Cushings disease
- ACTH-releasing pituitary tumor
- same symptoms as Cushing’s syndrome with high ACTH and androgens
Congenital Adrenal Hyperplasia
- 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
