Steroid Biosynthesis

Question 1

What is the enzyme converting cholesterol to pregnenolone?

Answer 1

desmolase

Question 2

What is the precursor for all steroid hormones?

Answer 2

progesterone

Question 3

What are the corticosteroids mentioned?

Answer 3

aldosterone, cortisol

Question 4

What are the sex hormones mentioned?

Answer 4

testosterone, estradiol

Question 5

What positively regulates 20,22-desmolase?

Answer 5

ACTH, catalyzes the 1st (rate-limiting) step cholesterol -> pregnenolone

is found in all steriod producing tissues (adrenal, testes, ovary, placenta)

Question 6

What are the biochemical actions of ACTH?

Answer 6

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)

Question 7

Cortisol

Answer 7

• binds and activates glucocorticoid receptor (GR)
• increases gluconeogenesis and blood pressure (increases Na uptake in kidneys)
  anti-inflammatory

Question 8

Glucocorticoids and infant respiratory distress syndrome

Answer 8

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)

Question 9

Aldosterone

Answer 9

• binds and activates mineralocorticoid receptor (MR)
• increases Na and water retention
• raises blood pressure

Question 10

Testosterone

Answer 10

• binds and activates androgen receptor (AR)

- male sex hormone

Question 11

Congenital adrenal hyperplasia (CAH)

Answer 11

• women often present with hirsutism (excessive body hair, where hair doesnt usually grow)
• female patients also present with general oligomenorrhea (infrequent menstruation) or infertility

Question 12

Classical CAH

Answer 12

• simple virilizing: ambiguous genitalia in females

- salt wasting: dehydration, vomiting, diarrhea, if untreated can be fatal

Question 13

Non-classical CAH

Answer 13

• milder than classical CAH
• androgen excess can cause precocious puberty in either sex
• males often undiagnosed and asymptomatic

Question 14

What are the genes involved in CAH cases?

Answer 14

• 95% of CAH cases involved the gene for 21-hydroxylase

- 5% involve the gene for 11beta-hydroxylase

Question 15

What will a mutation in 11beta-hydroxylase cause?

Answer 15

• a buildup of corticosterone precursors
• leads to a massive shift of excess androgen production (DHEA, androstenedione, TESTOSTERONE, dihydrotestosterone, estrogens)

Question 16

What causes hypertension in CAH?

Answer 16

• 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)

Question 17

What happens with 21alpha-hydroxylase mutation?

Answer 17

• reduced cortisol synthesis
• hyperplasia of the renal cortex
• elevated ACTH levels
• increased progesterone
• increase 17alpha-hydroxypregnenolone
• increase 17alpha-hydroxyprogesterone

Question 18

What is the most important biochemical intermediate used as a substrate to produce other steroid hormones?

Answer 18

pregnenolone

Question 19

What are more rare forms of CAH caused by?

Answer 19

CYP17A1 (aka 17alpha-hydroxylase, 17,20-lyase)

Question 20

What does 17,20-lyase do?

Answer 20

enzyme that converts progesterone to testosterone

17a-hydroxypregnenolone -> dehydroepiandrosterone (DHEA)
17a-hydroxyprogesterone -> androstenedione

Question 21

What stimulates aromatase to convert androstenedione to estrone, and testosterone to estradiol?

Answer 21

FSH

Question 22

What inhibits FSH and LH secretion from the pituitary gland?

Answer 22

in females: progesterone

in males: testosterone (inhibits LH) inhibin (inhibits FSH)

Question 23

Where is 25-hydroxycholecalciferol formed?

Answer 23

exclusively in the liver by 25-hydroxylase, coded by the CYP2R1 gene

NOTE: key in vitamin D regulation