Biochem: Sex Hormones

Question 1

Where do LH and FSH bind in male reproductive physiology?

Answer 1

LH binds leydig cells encouraging testosterone production

FSH binds sertoli cells encouraging sperm production and Androgen Binding Protein (ABP) production

Question 2

Describe the formation of Testosterone in Leydig cells after LH binds.
(6 steps: 1 transport protein, 4 enzymes)

Answer 2

1. LH binds raising cAMP levels and liberating cholesterol from the cholesterolesters.
2. Cholesterol travels into the mitochondria using the Steroidogenic Acute Regulatory (StAR) protein
3. In the mitochondrion cholesterol is converted to pregnenolone by the enzyme P450scc
4. Pregnenolone is converted to DHEA by the enzyme CYP 17 back in the cytosol
5. DHEA is converted to androstenedione using the enzyme 3-beta hydroxysteroid dehydrogenase (HSD)
6. Androstenedione is converted to testosterone (T) by the enzyme C17 dehydrogenase (DH)

Question 3

Enzyme that converts T into Dihydrotestosterone (DHT) and what is DHT’s function?

Answer 3

5-alpha reductase
DHT is more potent than T in peripheral tissues (outside the testes) and is mainly used for development of secondary sex characteristics

Question 4

How is testosterone production different in the leydig cells vs. adrenal cortex?

Answer 4

In the adrenal cortex, the pathway only reaches as far as androstenedione and must travel to extra-adrenal tissue (mainly testes) to be fully converted to T.

Question 5

Main protein that transports T in circulation.

Answer 5

Sex Hormone Binding Globulin (SHBG)

Question 6

List 3 non-genomic effects of T.

Answer 6

Closes Cl- channels
Activates MAPK
Increases intracellular Calcium

Question 7

Pathology of Klinefelter Syndrome.

Answer 7

47XXY
Leads to decreased T production and an Increase in LH production due to lack of negative feedback.

This leads to increased estrogen production which stimulates SHBG production. SHBG binds T and further decreases serum T levels

Question 8

Why do Klinefelter patients grow taller than average?

Answer 8

T encourages closure of growth plates and this is delayed in Klinefelter syndrome.

Question 9

Name the 3 estrogens

Answer 9

Estrone (E1)
Estradiol (E2)
Estriol (E3)

Question 10

Explain how Theca cells produce testosterone in the ovary in response to LH binding its receptor.

Answer 10

1. LH binds raising cAMP levels and liberating cholesterol from the cholesterolesters.
2. Cholesterol travels into the mitochondria using the Steroidogenic Acute Regulatory (StAR) protein
3. In the mitochondrion cholesterol is converted to pregnenolone by the enzyme P450scc
4. Pregnenolone is converted to DHEA by the enzyme CYP 17 back in the cytosol
5. DHEA is converted to androstenedione using the enzyme 3-beta hydroxysteroid dehydrogenase (HSD)
6. Androstenedione is converted to testosterone (T) by the enzyme C17 dehydrogenase (DH)

(exact same as Leydig Cells in the testes)

Question 11

What additional precursor can be turned into androstenedione other than DHEA in the thecal cells?

Answer 11

Progesterone using the CYP17 enzyme

Question 12

Once T diffuses from the thecal cell to the granulosa cells, how is it converted into E2?

Answer 12

Using the enzyme CYP19A1 (aromatase)

Question 13

What action does FSH have on the Granulosa cells.

Answer 13

1. FSH binds increasing cAMP levels
2. Androstenedione diffuses into granulosa cells from thecal cells and is converted to E1 by aromatase.
3. E1 is converted to E2 using HSD17B1

Question 14

What non-genomic factors are influenced by estrogen binding?

Answer 14

Breast development

Increased sensitivity of the Ant. Pit. to GnRH

Question 15

Enzyme that converts pregnenelone into progesterone.

Answer 15

3-beta hydroxysteroid dehydrogenase

same enzyme that converts DHEA into andronstenedione

Question 16

Main actions of progesterone

Answer 16

Maintain uterine lining
Prevent uterine contraction
Negative feedback for LH secretion