Estrogen production in reproductive-age women

Where is estrogen coming from in premenopausal women?

(1)The ovaries (follicle granulosa cells) before ovulation (follicular phase) are the main source of estrogen  (predominantly ESTRADIOL), which functions as a circulating hormone

(2) A small amount of estrogen is produced in peripheral tissue (E.g. skin, fat, muscle) by the conversion of circulating androgens (via aromatase enzyme)

(3)Theplacenta produces ESTRIOL during pregnancy

Feedback mechanism of estrogenproduction during reproductive cycle

ESTRADIOL production is under the cyclical endocrine control of two PITUITARY gonadotrophins, LH and FSH - which are released by hypothalamic GnRH(which is subject to negative estrogen feed-back from the ovaries )

• By negative-feedback - high-level Estrogen causes a decrease in FSH/LH production by inhibiting hypothalamic GnRH (Gonadotropin Releasing Hormone) production.

FSH/LH ▲ ➔ Estrogen ▲ 

Estrogen ▲ ▲ ▲  ➔  GnRH ▼ ➔  FSH/LH▼➔  Estrogen ▼

(Rising levels of estrogen in the blood begins follicle/egg development)

Luteinizing hormone (LH) -binds with LH receptors tostimulate follicle thecal cells to produce mainly ANDROSTENEDIONE,which is supplied to the neighboring follicle granulosa cells as a substrate with which to make ESTRADIOL;

Follicle-stimulating hormone (FSH)

• FSH stimulates the growth of immature ovarian follicles-by pronounced of granulosa cells.
• FSH stimulatesgranulosa cells of ovarian follicle (a collection of fluid around eggs) to secreteestrogens - mainly ESTRADIOL;
• Follicle granulosa cellshave FSH-sensitivearomatase activity and proliferate in response to estrogens:
  • Inhibited by androgens;
  • FSH regulates transcription of the aromatase gene (CYP19A1) in ovarian granulosa cells.
  • Substrate ANDROSTENEDIONE is supplied by ovarian theca cells and is converted to ESTRONE by aromatase - followed by conversion of ESTRONE to ESTRADIOL▲by 17β-HSD enzyme.
  • Estrogenstimulates the uterine endometrium to proliferate and to synthesize PROGESTERONE receptors (PR's) ▲ in the cytosol;
  • After ovulation (2^nd half of menstrual cycle, called the luteal phase),estrogen▼ production/secretion from theovarian granulosa cellsdecreases;

The rise in ESTRADIOL causes expression of LH receptors ▲  on maturing follicles, which also indirectly increases ESTRADIOL▲  production.    By stimulating theca cells to provide more substrate ANDROSTENEDIONE. ESTRADIOL continues its positive feedback loop supplying LH receptors for LH activation to provide more ANDROSTENEDIONE substrate for additional estrogenproduction, until high estrogenlevels inhibit hypothalamic GnRH,causing a decrease in FSH production and a subsequent decrease in estrogenproduction;

Normal female estrogenproduction fluctuates during reproductive years

Normal, averageestrogen levels (measured in pg/ml) vary for a woman at different times throughout her reproductive years.

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