9. Steroid Biosynthesis

Question 1

What are secreted by the testis in response to FSH and LH respectively?

Answer 1

FSH stimulates inhibin.

LH stimulates testosterone.

Question 2

What enzyme is “the gatekeeper” between progesterone and testosterone?

Answer 2

17,20-lyase.

Question 3

What enzyme catalyzes the rate limiting step of steroid hormone biosynthesis?

Answer 3

Desmolase

Question 4

What inhibits gonadotropin releasing hormone from the hypothalamus in males and females respectively?

Answer 4

Males: testosterone.

Females: progesterone.

Question 5

In a patient with congenital adrenal hyperplasia, what is the result of a 17α-hydroxyprogesterone buildup?

Which versions of congenital adrenal hyperplasia could this be?

Answer 5

Excess androgen production, especially testosterone and dihydrotestosterone.

11β-hydroxylase deficiency/mutation.

Question 6

95% of congenital adrenal hyperplasia involves which gene?

The other 5% involves what gene?

Answer 6

21-hydroxylase.

11β-hydroxylase.

Question 7

How does adrenocorticotropic hormone increase the production of steroid hormones?

Answer 7

ACTH upregulates desmolase.

Question 8

What are the symptoms associated with congenital adrenal hyperplasia?

Answer 8

Hirsutism.

General oligomenorrhea.

Infertility.

Simple virilizing.

Salt wasting (with dehydration, vomiting, and diarrhea).

(Non-classical is milder, and may cause only precocious puberty.)

Question 9

What receptor is bound and activated by cortisol?

Answer 9

The glucocorticoid receptor.

Question 10

What enzyme is upregulated by luteinizing hormone?

Answer 10

Desmolase.

Question 11

Describe the regulation of desmolase.

Answer 11

Desmolase is upregulated by ACTH and LH.

Question 12

What is the significance of glucocorticoids in premature infants?

Answer 12

A burst of glucocorticoids during delivery stimulates the production of surfactant.

Question 13

How are follicle stimulating hormone and luteinizing hormone inhibited from the pituitary gland in males?

Answer 13

Inhibin inhibits follicle stimulating hormone.

Testosterone inhibits luteinizing hormone.

Question 14

What are the short and long-term effects of adrenocorticotropic hormone?

Answer 14

Short-term: stimulates lipoprotein uptake into cortical cells and increases bioavailability of cholesterol in the adrenal cortex. (Brings the building blocks for steroid hormone synthesis)

Long-term: stimulates the transcription of the genes coding for steroidogenic enzymes.

Question 15

What are the general functions of cortisol?

Answer 15

↑ Gluconeogenesis.

↑ Blood pressure.

↓ Inflammation.

Question 16

What symptoms do we see in patients with 21-hydroxylase deficient congenital adrenal hyperplasia?

Answer 16

Salt wasting, due to lack of aldosterone.

Ambiguous genitalia in females.

Question 17

How are follicle stimulating hormone and luteinizing hormone inhibited from the pituitary gland in females?

Answer 17

Progesterone inhibits follicle stimulating hormone and luteinizing hormone.

Estradiol inhibits FSH and LH in the early to mid follicular phase, but stimulates FSH and LH in the late follicular phase.

Question 18

What enzyme is stimulated by follicle stimulating hormone?

What reactions are catalyzed by this enzyme?

Answer 18

Aromatase

Androstenedione -> Estrone

Testosterone -> Estradiol

Question 19

What are the two steroid hormone blood transporter proteins mentioned in this lecture?

Where are they made?

Answer 19

Corticosteroid binding globulin (CBG).

Sex steroid binding globulin (SHBG).

They are made in the liver.

Question 20

Where is cholecalciferol converted to 25-hydroxycholecalciferol?

What enzyme facilitates this reaction?

Answer 20

In the liver.

25-hydroxylase.

Question 21

What receptor is bound and activated by testosterone?

Answer 21

The androgen receptor.

Question 22

What receptor is bound and activated by aldosterone?

Answer 22

The Mineralcorticoid receptor

Question 23

How are estradiol and progesterone stimulated to be released from the ovaries?

Answer 23

FSH and LH stimulate estradiol production in the follicular phase, and progesterone production in the luteal phase.

Question 24

What two corticosterone precursors are increased in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency?

Answer 24

11-deoxycorticosterone

17α-hydroxyprogesterone

Question 25

In a patient with congenital adrenal hyperplasia, what would be the effects of a buildup of 11-deoxycorticosterone?

Which version of congenital adrenal hyperplasia would this be?

Answer 25

11-deoxycorticosterone acts on aldosterone receptors in an unregulated fashion, increasing sodium uptake, water retention, and potassium excretion.

This would be 11β-hydroxylase deficiency/mutation.

Question 26

What reaction is catalyzed by desmolase?

Answer 26

Cholesterol -> pregnenolone.

Question 27

What are the general functions of aldosterone?

Answer 27

↑ Na+ and H2O retention

↑ Blood pressure

Question 28

What three compounds build up in patients with 21-hydroxylase deficient congenital adrenal hyperplasia?

Answer 28

Progesterone.

17α-hydroxypregnenolone.

17alpha-hydroxyprogesterone.

Question 29

What are the primary symptoms of 17,20-lyase deficient congenital adrenal hyperplasia?

Answer 29

Males: pseudohermaphroditism, underdeveloped genitalia.

Both sexes: reduced or absent puberty, lack of development of secondary sexual characteristics, childlike appearance in adulthood if left untreated.

[Note: 17,20-lyase deficiency alone does not affect mineralcorticoid or glucocorticoid production. For that reason it does not cause adrenal hyperplasia or hypertension.]