Steroid Biosynthesis Flashcards
(23 cards)
What is the enzyme converting cholesterol to pregnenolone?
desmolase
What is the precursor for all steroid hormones?
progesterone
What are the corticosteroids mentioned?
aldosterone, cortisol
What are the sex hormones mentioned?
testosterone, estradiol
What positively regulates 20,22-desmolase?
ACTH, catalyzes the 1st (rate-limiting) step cholesterol -> pregnenolone
is found in all steriod producing tissues (adrenal, testes, ovary, placenta)
What are the biochemical actions of ACTH?
short term (seconds): stimulates lipoprotein uptake into cortical cells, increases bioavailability of cholesterol in adrenal cortex
long term (hours): stimulation of the transcription of the genes coding for steroidogenic enzymes (P450scc enzyme)
Cortisol
- binds and activates glucocorticoid receptor (GR)
- increases gluconeogenesis and blood pressure (increases Na uptake in kidneys)
anti-inflammatory
Glucocorticoids and infant respiratory distress syndrome
normal term infants:
- burst of glucocorticoids during delivery
- alters lung structure
- stimulates production of surfactant (allowing lung expansion)
premature infants:
- process is defective, leads to infant respiratory distress syndrome
- > prevented by giving mothers glucocorticoids (betamethasone, dexamethasone)
Aldosterone
- binds and activates mineralocorticoid receptor (MR)
- increases Na and water retention
- raises blood pressure
Testosterone
- binds and activates androgen receptor (AR)
- male sex hormone
Congenital adrenal hyperplasia (CAH)
- women often present with hirsutism (excessive body hair, where hair doesnt usually grow)
- female patients also present with general oligomenorrhea (infrequent menstruation) or infertility
Classical CAH
- simple virilizing: ambiguous genitalia in females
- salt wasting: dehydration, vomiting, diarrhea, if untreated can be fatal
Non-classical CAH
- milder than classical CAH
- androgen excess can cause precocious puberty in either sex
- males often undiagnosed and asymptomatic
What are the genes involved in CAH cases?
- 95% of CAH cases involved the gene for 21-hydroxylase
- 5% involve the gene for 11beta-hydroxylase
What will a mutation in 11beta-hydroxylase cause?
- a buildup of corticosterone precursors
- leads to a massive shift of excess androgen production (DHEA, androstenedione, TESTOSTERONE, dihydrotestosterone, estrogens)
What causes hypertension in CAH?
- 11-deoxycorticosterone accumulates abnormally (MR agonist)
- disregulated salt and water balance -> promotes Na and water retention -> lowers plasma K concentration
NOTE: 11-deoxycorticosterone has much higher affinity for MR (than 11-deoxycortisol), to cause hypertension (HTN associated with MR activity due to increased aldosterone)
What happens with 21alpha-hydroxylase mutation?
- reduced cortisol synthesis
- hyperplasia of the renal cortex
- elevated ACTH levels
- increased progesterone
- increase 17alpha-hydroxypregnenolone
- increase 17alpha-hydroxyprogesterone
What is the most important biochemical intermediate used as a substrate to produce other steroid hormones?
pregnenolone
What are more rare forms of CAH caused by?
CYP17A1 (aka 17alpha-hydroxylase, 17,20-lyase)
What does 17,20-lyase do?
enzyme that converts progesterone to testosterone
17a-hydroxypregnenolone -> dehydroepiandrosterone (DHEA)
17a-hydroxyprogesterone -> androstenedione
What stimulates aromatase to convert androstenedione to estrone, and testosterone to estradiol?
FSH
What inhibits FSH and LH secretion from the pituitary gland?
in females: progesterone
in males: testosterone (inhibits LH) inhibin (inhibits FSH)
Where is 25-hydroxycholecalciferol formed?
exclusively in the liver by 25-hydroxylase, coded by the CYP2R1 gene
NOTE: key in vitamin D regulation
