Steroid hormones (2-1)

Question 1

Role of PNMT? What increases transcription of PNMT?

Answer 1

Converts epinephrine to norepinephrine; cortisol increases transcription. A decrease in cortisol leads to a decrease in epinephrine (Addison’s dx)

Question 2

Role of StAR protein?

Answer 2

To transport cholesterol into the inner mitochondrial membrane

Question 3

After cholesterol is synthesized to pregnenolone, to which organelle is it transported to, to continue the pathway?

Answer 3

Smooth ER

Question 4

Androstenedione is a precursor to _____

Answer 4

Testosterone (via 17-ketoreductase)

Question 5

Describe electron flow, from NADPH to cytochrome P-450 hydroxylase

Answer 5

NADPH transfers 2 electrons to adrenodoxin reductase. Then, the electrons are passed on to adrenodoxin. Finally, Adrenodoxin passes them on to cytochrome P-450 hydroxylase.

Question 6

Describe 5 alpha-reductase deficiency

Answer 6

Testosterone cannot be converted to DHT; a genetic male looks like a female, from birth until puberty. After puberty, testosterone production is ramped up, returning the phenotype to normal.

Question 7

Describe the overall actions of glucocorticoids

Answer 7

To increase production of glucose while inhibiting all other pathways not involved in glucose production. This causes HYPERGLYCEMIA and HYPERINSULINEMIA.

Question 8

What is characteristic of people with Addison’s disease / hypocortism?

Answer 8

Plasma adrenaline levels have been shown to be reduced

Question 9

Cause of Cushing’s dx?

Answer 9

Elevated levels of cortisol! May also lead to increased amounts of male sex hormone, because of overactive adrenal glands

Question 10

What is the obesity and hyperglycemia in people with Cushing’s dx, due to?

Answer 10

Due to the insulin-resistant muscle and liver, and also due to hyperinsulinemia (down-regulates insulin receptors)

Question 11

What is the HTN in Cushing’s dx, due to?

Answer 11

Due to the activation of the aldosterone receptor by excess amounts of cortisol

Question 12

How does 11-beta-HSD protect mineralocorticoid receptors from the high concentrations of glucocorticoids?

Answer 12

11-B-HSD converts cortisol, which binds the mineralocorticoids, to cortisone, which doesn’t bind them.

Question 13

What are the effects of increased aldosterone, on Na+ and K+?

Answer 13

An increase in K+ excretion and Na+ reabsorption is seen; thus, an increase in BP is also seen.

Question 14

How is renin production stimulated?

Answer 14

It is stimulated in the kidneys, when there is a decrease in BP

Question 15

What causes congenital adrenal hyperplasia, and why?

Answer 15

An excess amount of ACTH in the blood causes CAH because there are low levels of epinephrine and a lack of (-) feedback inhibition

Question 16

3-beta hydroxysteroid dehydrogenase deficiency (CAH)

Answer 16

• Highest on the overall pathway; perhaps the most pathologic.
• AR dx with no gluco/mineralocorticoids, androgens or estrogens
• Salt excretion in urine
• Patients have female-like genitalia

Question 17

17-alpha hydroxylase deficiency (CAH)

Answer 17

• No sex hormones or cortisol are produced

- Increased production of mineralocorticoids (aldosterone) -> Na+ and fluid retention; thus, hypertension.

Question 18

21-alpha hydroxylase deficiency (CAH)

Answer 18

• Most common form of CAH
• Gluco- and Mineralocorticoids are absent
• Overproduction of androgens -> masc. of external genitalia in females / early virilization in males

Question 19

11-beta-1 hydroxylase deficiency (CAH)

Answer 19

• Decrease in cortisol, aldosterone and corticosterone

- Increase in fluid retention, which suppresses the renin/angiotensin system, causing low-renin hypertension

Question 20

3-beta hydroxysteroid dehydrogenase deficiency

Answer 20

• Requires NAD+ and is NOT a cytochrome p450 enzyme (while the rest are)
• Deficiency affects production of:
• – Cortisol: hypoglycemia, epi deficiency
• – Aldosterone: low BP
• – Androgens: female genitalia in males, female infertility

Question 21

17-alpha hydroxylase / 17,20-lyase deficiency

Answer 21

• Aldosterone levels will be high, so HTN is seen
• Overproduction of ACTH causes adrenal hyperplasia
• Males and females will be sterile; feminization of males, seen

Question 22

21-alpha hydroxylase deficiency

Answer 22

• No cortisol is produced, leading to hypoglycemia
• No aldosterone produced, leading to hypotension
• Adrenal glands produce excess androgens

Question 23

11-beta hydroxylase deficiency

Answer 23

• Adrenal glands produce excess androgens

- Although both sexes will be virilized (males, prematurely so), both sexes will be infertile.