Adrenal physiology Flashcards
zona glomerulosa: product
aldosterone
zona fasciculata: product(s)
cortisol
some androgens
zona reticularis: product(s)
androgens
some cortisol
ACTH binds to what receptor?
MC2R
which enzyme is responsible for cleaving cholesterol? what is the product?
cholesterol desmolase
pregnenolone
what are the biosynthetic products of mineralocorticoid synthesis?
cholesterol pregnenolone progesterone DOC corticosterone 18-OH corticosterone aldosterone
what are the biosynthetic products of glugocorticoid synthesis?
cholesterol pregnenolone 17-OH pregnenolone 17-OH progesterone 11-deoxycortisol cortisol
what are the biosynthetic products of androgen synthesis?
cholesterol pregnenolone 17-OH pregnenolone DHEA androstenedione testosterone (formation occurs in testes)
what is the rate limiting conversion step of glucocorticoid biosynthesis?
which enzyme is this?
conversion of cholesterol into pregnenolone
cholesterol desmolase
what enzyme allowed formation of DHEA from 17-OH pregnenolone?
17a hydroxylase
17-20 lyase
which enzyme is responsible for converting DHEA to androstenedione?
3B-hydroxysteroid dehydrogenase
ACTH affects which rate limiting step of glucocorticoid synthesis?
cholesterol desmolase
how does cortisol maintain and increase plasma glucose levels?
- increased gluconeogenesis
- decreased glucose use by most cells
which compounds have ‘slight’ mineralocorticoid activity?
11-deoxycorticosterone (DOC)
corticosterone
which synthetic mineralocorticoid is used to treat primary adrenal insufficiency?
fludrocortisone
regulation of aldosterone synthesis
- angiotensin II binds AII-receptor in zone glomerulosa cells - increase in intracellular calcium leads to increase in expression of StAR and cholesterol desmolase
- elevated blood potassium depolarizes zona glomerulosa cells increases intracellular calcium
functions of aldosterone
where are the mineralocorticoid receptors?
- maintain sodium, potassium, and water (blood volume) balance
- conserve sodium during sweating
- prevents loss of sodium in stool
- distal convoluted tubule and collecting ducts, distal colon, sweat glands, salivary gland epithelial cells
what is AME? what is the cause? why does this occur?
apparent mineralocorticoid excess - rare genetic disease
caused by inactivation of 11B-HSD2
cortisol can bind mineralocorticoid receptor
what is the physiological importance of 11B-HSD type 1 and 11B-HSD type 2?
- 11B-HSD1 converts cortisone (inactive) to cortisol (active)
- 11B-HSD2 converts cortisol (active) to cortisone (inactive)
- 11B-HSD1 is abundant in liver, adipose tissue, brain, and lung
- 11B-HSD2 is abundant in kidney, colon, salivary glands
hypercortisolism can lead to saturation of what enzyme?
11B-HSD2
17a-hydroxylase deficiency: high or low?
mineralocorticoids potassium cortisol androgens BP
HIGH mineralocorticoids LOW potassium LOW cortisol LOW androgens HIGH BP
what is the diagnostic test / lab seen in 17a-hydroxylase deficiency?
increased 17-OH progesterone
what is the presentation for 17a-hydroxylase deficiency?
- XY: ambiguous genitalia, undescended testes, virilize inadequately at puberty
- XX: lack secondary sexual development
21-hydroxylase deficiency: high or low?
mineralocorticoids potassium cortisol androgens BP
LOW mineralocorticoids HIGH potassium LOW cortisol HIGH androgens LOW BP
what is the presentation for 21-hydroxylase deficiency?
- XX infants can have male genitalia (virilization)
- salt wasting crisis
- precocious puberty
11B-hydroxylase deficiency: high or low?
mineralocorticoids deoxycorticosterone (DOC) potassium cortisol androgens BP
LOW mineralocorticoids HIGH deoxycorticosterone (DOC) LOW potassium LOW cortisol HIGH androgens HIGH BP
11B-hydroxylase deficiency: presentation
virilization
high dose dexamethasone test: ACTH and cortisol response in:
pituitary hypersecretion of ACTH
50% reduction in ACTH and cortisol
high dose dexamethasone test: ACTH and cortisol response in:
adrenal adenoma
no reduction in cortisol or ACTH
high dose dexamethasone test: ACTH and cortisol response in:
ectopic ACTH production
no reduction in cortisol or ACTH
high dose dexamethasone test: ACTH and cortisol response in:
iatrogenic Cushing’s syndrome
no reduction in cortisol or ACTH
what enzyme converts tyrosine to DOPA?
tyrosine hydroxylase (rate limiting)
what enzyme converts NE to EPI?
PNMT
what converts EPI to metanephrine?
COMT
what converts NE to normetanephine?
COMT
