BCM - Steroid Biosynthesis

Question 1

How does the body respond to short term stress?

Answer 1

Sympathetic stimulation of the adrenal medulla, causing secretion of epinephrine and norepinephrine

Question 2

How does the body respond to long term stress?

Answer 2

Glucocorticoid and Mineralocorticoid secretion from the adrenal cortex

Question 3

What is PXR?

Answer 3

Xenobiotic nuclear receptor

It is an adopted orphan receptor (we used to not know what the receptor did, now we do)

Question 4

What does activation of PXR do and what is its ligand?

Answer 4

PXR promotes the CYP3A4 gene after St. John’s wart activates the receptor

CYP3A4 is an enzyme that metabolizes 60% of all prescribed drugs

Question 5

What happens to the CYP3A4 metabolized drugs?

Answer 5

They get excreted in the bile

Question 6

What are steroid hormones derived from?

Answer 6

Cholesterol

Question 7

What is desmolase?

Answer 7

Desmolase (aka CYP 450scc) is an enzyme that converts Cholesterol into Pregnenolone, the first step and rate-limiting step in synthesis of steroid hormones

Desmolase is positively regulated by ACTH

Question 8

What happens in the process of steroid synthesis after pregnenolone is made?

Answer 8

Pregnenolone is converted to Progesterone

Then progesterone can either be converted into corticosteroids (aldosterone/cortisol) or sex hormones (testosterone/estradiol)

Question 9

Where is desmolase found?

Answer 9

Desmolase enzyme can be found in all the steroid producing tissues (adrenal, ovaries, testes, placenta)

Question 10

How is cortisol secretion regulated?

Answer 10

Cortisol provides negative feedback to the anterior pituitary (inhibiting ACTH secretion) and the Hypothalamus (inhibiting CRH secretion)

Question 11

What are the SHORT TERM actions of ACTH?

Answer 11

SHORT TERM = seconds

Stimulates lipoprotein uptake into cortical cells and increases bioavailability of cholesterol in adrenal cortex

Question 12

What are the LONG TERM actions of ACTH?

Answer 12

LONG TERM = hours

Stimulates transcription of key enzymes needed for steroid hormone synthesis, including:

• CYP450scc (Desmolase)
• Steroid 11(beta)-hydroxylase
• Associated electron transfer proteins

Question 13

What happens in a adrenal cortex cell if it is cancerous?

Answer 13

PKA is constitutively active, causing cell proliferation and cortisol synthesis

Question 14

What is the enzyme responsible for the conversion of Pregnenolone to Progesterone?

Answer 14

3(beta) - Hydroxysteroid Dehydrogenase

AKA 3(beta)-HSD

Question 15

What does cortisol do?

Answer 15

Increases blood pressure, anti-inflammatory, promotes gluconeogenesis, immunosuppression

Question 16

What is Infant Respiratory Distress syndrome?

Answer 16

Process of surfactant production is defective due to lack of glucocorticoids

With children of normal term births, the infant recieves a burst of glucocorticoids during delivery, altering the lung structure so that it can produce surfactant, allowing the lung to expand

Question 17

What are classical presentations of Congenital Adrenal Hyperplasia?

Answer 17

CAH classical presentations include ambiguous genitalia in females, and salt wasting (resulting in dehydration, vomiting, diarrhea)

Question 18

Which genes are typically affected in Congenital ADrenal hyperplasia?

Answer 18

CAH involves mutation of the 21-hydroxylase enzyme 90-95% of the time

5% involves mutation of 11(beta)-hydroxylase enzyme

Question 19

What happens when 11-beta-hydroxylase enzyme is mutated?

Answer 19

11 beta hydroxylase enzyme is required in the pathway for Aldosterone synthesis and the pathway for Cortisol synthesis

Mutation in this enzyme causes buildup of precursors

Results in excess androgen production (male sex hormones

Results in 11-deoxycorticosterone accumulation (which is a mineralocorticoid receptor agonist; promotes sodium and water rentention as aldosterone normally would HYPERTNSION!!)

Question 20

What happens with 21 hydroxylase mutation form of CAH?

Answer 20

Accumulation of Progesterone and 17 alpha hydroxypregnenalone and 17 alpha progesterone

Lack of aldosterone causes salt wasting and females have obvious genital ambiguity