Sex steroid synthesis

Question 1

Androgen synthesis enzymes (4)

TESTOSTERONE

Answer 1

1. P450 SCC
2. 17 α hydroxylase / C17-20 lyase
3. 17ß hydoxysteroid DH

⇔

4. 3ß hydoxysteroid DH / 5-4 isomerase

Question 2

Androgen Synthesis Enzymes (5)

DIHYDROTESTOSTERONE

Answer 2

1. P450 SCC
2. 17 α hydroxylase / C17-20 lyase
3. 17ß hydoxysteroid DH

⇔

4. 3ß hydoxysteroid DH / 5-4 isomerase
5. 5α reductase

Question 3

Androgen Synthesis Enzymes (5)

ESTRADIOL

Answer 3

1. P450 SCC

2. 17 α hydroxylase / C17-20 lyase
3. 17ß hydoxysteroid DH

⇔

4. 3ß hydoxysteroid DH / 5-4 isomerase
5. aromatase

P450 complex: uses 3NADPH and 3 O₂

found in many tissues: brain, skin, fat

Question 4

Testosterone (4)

Answer 4

1. Synthesis in testes
2. GnRH regulation (long loop negative feedback)
3. Stimulates spermatogenesis
4. Sexual differentiation: Wolffian stimulation

Question 5

1. DHT
2. Androstanediol
3. Estradiol
4. Estrone
5. Estriol

Answer 5

1. Potent, targets prostate and parts of male genitalia
2. potent, from DHT via 3α reductase
3. from tesosterone via aromatase
4. from androstenedione via aromatase
5. From DHEA -> estrone via 16α hydroxylase & aromatase

Question 6

FSH and LH on testosterone synthesis

Answer 6

LH: stimulates Leydig cells to activate adenylate cyclase

FSH: induces Leydig cells to make more LH receptors

Acts on sertoli cells to make ABP (helps to “bate” the seminiferous tubules in very high levels of hormone)

Sertoli cells produce inhibin that acts on FSH release in pituitary

Question 7

Hormone transport

1. Testosterone
2. DHT
3. Estradiol
4. Estrone
5. Progesterone

Answer 7

1. TeBG aka SHBG, albumin (weak)

1-3% free, *strong affinity, long half-life

2. TeBG
3. TeBG (weak)
4. albumin
5. CBG

Question 8

Steroids of the Ovary (3)

Estrone

Answer 8

1. Progesterone (corpus luteum)
2. 17ß Estradiol (from TESTOSTERONE)
3. Estriol (during pregnancy)
4. Estrone (postmenopausal women) adrenal glands

estriol and estrone made from ANDROSTENEDIONE

Question 9

Purpose for steroid synthesis in Theca cells vs granulosa cells

Answer 9

Need to separate production of progesterone & estradiol in order to control levels

Theca cells: NO AROMATASE

progesterone –> testosterone

Granulosa cells: NO 17 HYDROXYLASE

—> PROGESTERONE secreted

Question 10

Steroid synthesis in utero

Answer 10

1. Estriol made in the PLACENTA from fetus’ adrenal precursor DHEA

2, Cortisol made in ADRENAL from placental progesterone

Question 11

Degradation

Answer 11

1. Make glucuronide or sulfate derivatives
2. Liver degradation of progesterone is so efficient that oral progesterone is ineffective in humans

*synthetic progestins are used instead

Question 12

Polycystic ovarian syndrome (PCOS)

Stein-Leventhal syndrome

1. Cause
2. Characteristics (4)

Answer 12

1. Excess production of androgens
2. hirsutism (excessive hair growth in women)
   - obesity
   - irregular menses
   - impaired fertility

Question 13

_Ovarian Hormone Diseases _

1. Leydig cell and arrhenoblastoma tumors
2. Granulosa-theca cell tumors
3. Intraovarian adrenal rests
4. Hydratiform mole (malignant- choriocarcinoma)

Answer 13

1. testosterone
2. estrogens
3. cortisol
4. hCG

Question 14

Osteoporosis

Answer 14

1. Since ovarian estrogen synthesis stops at menopause, estrone is made
2. Weak estrogen from adrenal androstenedione

may not be sufficient to maintain bone mass

Question 15

Tamoxifen

(3)

Answer 15

1. Estrogen antagonist
2. induces a diff conformational change after binding to receptor = bone saving effects of estradiol
3. in breast cancer, prevents estradiol binding to receptor (this prevents growth stimulation)

Question 16

DES

(4)

Answer 16

1. Estrogen agonist. synthetic estrogen
2. marketed to prevent miscarriage and increase live deliveries
3. Daughters: increased risk for
   - clear cell adenocarcinoma of vagina and cervix
   - reproductive tract structural differences
   - pregnancy complications
   - infertility
4. Sons” increased risk for epididymal cysts