Sex hormones (Ben) Flashcards
What is the starting molecule for synthesis of all sex hormones?
DHEA
What 3 reactions does 17-hydroxy steroid dehydrogenase (17OHSDH) catalyze?
- DHEA → androstenediol
- androstenedione → testosterone
- estrone → estradiol
- All creating more active sex hormone products than the substrates
What cofactor does 17OHSDH use?
NADPH
What are the 2 androgen reactions catalyzed by 3OHSDH?
What co-factor is used?
- DHEA → androstenedione
- androstenediol → testosterone
- using NAD
What 2 reactions does aromatase catalyze?
- androstenedione → estrone
- testosterone → estradiol
What other androgen can be formed from testosterone?
Via what enzyme + cofactor?
5α-dihydrotestosterone
- via 5α reductase
with NADPH
What are the 3 isoforms of 17OHSDH?
Where are they + what do they catalyze?
- I - in cytosol of placenta, ovaries, adipose tissue
- estrone —> estradiol (NADPH)
- II - in ER of liver, intestine, and placenta
- oxidates/deactivates testosterone + estradiol (NAD)
- III - in ER of testis
- androstenedione —> testosterone (NADPH)
What cell type is the major site of testosterone synthesis?
What molecular signals stimulate synthesis + how?
Leydig Cells
- luteinizing hormone + hCG
- increase cAMP leading to activation of testosterone synthesis mechanisms
What enzyme/activity do Leydig cells lack?
And how does this influence their steroid production?
P45021
21-OHase activity
- keeps reactions moving towards androgens from pregnenolone
How does dihydrotestosterone differ from testosterone?
- binds to testosterone receptors more efficiently + its specific receptor is a better inducer
- can not be converted back to estrogens
Where is the aromatase reaction located?
Cell types + intracellular location.
in ovaries, placenta, adipose tissue, and bones
in the sER
What is the 2 cell theory in relation to estrogen production?
What 2 cell types are involved and what do they make?
-
Theca Interna - produce weak androgens from cholesterol
- 17-OHase, 17,20 Lyase
- no P450c21, 17-OHSDH, aromatase
-
Granulosa Cells - produce estradiol from androstenedione
- 17-OHSDH, aromatase
- no 17-OHase or 21-OHase
What hormones stimulate each of the two types of ovary cells necessary for estrogen production?
- Theca interna cells - luteinizing hormone (LH)
- Granulosa cells - follicle-stimulating hormone (FSH)
What happens to the two types of estrogen-producing cells in the ovary during the luteal phase?
- theca cells - lose 17-OHase/17,20 lyase activity
- granulosa cells - lose aromatase activity
- both switch to just producing progesterone from cholesterol
What is the common condition resulting in ovarian cysts?
How does it occur?
What non ovary-related symptoms is it associated with?
Polycystic Ovarian Syndrome
- via hyperandrogenism when theca cells increase + express more LH receptors —> androgen increase
- causes lack of ovulation and antral follicle retention (=cysts)
- associated with obesity + insulin resistance
What is the name for the estrogen-like compounds which can have tissue-specific actions?
Describe their action.
SERMs
(Selective Estrogen Receptor Modulators)
- interact with estrogen receptors + induce conformational change
- depending on tissue, can be agonist OR antagonist
What is an important synthetic SERM?
What are its actions?
What are its negative side effects?
Tamoxifen
- agonist in bones - prevents osteoporosis
- antagonist in breast tissue - breast cancer therapy
- side effect: partial agonist in endometrium - increases endometrial cancer risk
Name an important endogenous SERM.
What are its effects?
27-OH-Cholesterol
- promotes breast cancer proliferation
- decreases bone density
- increases risk of cardiovascular disease
What is the sex hormone synthesis function of the placenta?
Produces estradiol
- acts like a granulosa cell
- uses DHEA-sulfate from maternal/fetal adrenal cortex
What does the placenta lack for steroid hormone synthesis that forces it to rely on fetal/maternal precursors?
SF-1 (Steroidogenic Factor 1)
What sex hormone is primarily created in the fetal liver + adrenal cortex and is an even stronger version than any synthesized in adults?
Estriol
- stronger estrogen than estradiol
