TESTOSTERONE production / secretion in Men

Source of TESTOSTERONE production / secretion :

• >95% of circulating TESTOSTERONE secretedby the Lehdig cells of the testes (6-8mg/day)
• A small amount produced by adrenal cortex

TESTOSTERONE production decreases steadily with age (called Andropause) – with a concurrent increase in estrogen levels;

• TESTOSTERONE and estrogen are antagonists – and one particular estrogen, ESTRADIOL, is known to turn on the BCL2 cancer gene, increasing the risk of prostate cancer, when there is an inadequate amount of PROGESTERONE to counteract estrogen’s effect by stimulating the P53 cancer protection gene.
• TESTOSTERONE production decreases 1-2% /yr from age 30 to 70in the U.S.  Research by National Institutes of Health

Testes secrete higher levels of TESTOSTERONE in the morning and lower levels in the evening – interestingly this seems to be an intrinsic circadian rhythm, since it is not accompanied by changes in Luteinizing Hormone (LH).

TESTOSTERONE production / secretion control

•  GnRH from hypothalamus stimulates pituitary secretion of Luteinizing Hormone (LH) – which stimulates secretion of TESTOSTERONE from testes;

Hypothalamus → GnRH → Pituitary → LH → Testes → TESTOSTERONE

• By negative feedback, elevated levels of TESTOSTERONE suppress the release of hypothalamic GnRH – ESTRADIOL also suppresses GnRH;
• TESTOSTERONE production is also inhibited by: the inhibition of LH output,by circulating non-SHBG-bound TESTOSTERONE, and especially by DHT  (to provide negative feedback control of its own production, which is stimulated by LH); although, even in men, the major hormone involved in LH feedback is ESTRADIOL, not TESTOSTERONE; (SHBG is Sex Hormone Binding Globulin)

TESTOSTERONE is synthesized via two pathways:

• Δ4 pathway – From ANDROSTENEDIONE(via 17-βhydroxysteroid dehydrogenase enzyme) (preferred pathway)
•  or Δ5 pathway – From ANDROSTENEDIOL (itself synthesized from DHEA)

TESTOSTERONE production / secretion in Women

Source of TESTOSTERONE production is roughly:

• 50% from peripheral conversion
• 25% by the ovaries (thecal cells)
• 25% by adrenal cortex
• The placenta also produces TESTOSTERONE during pregnancy
• An overall total of ~ 0.3 mg TESTOSTERONE / day, ~1/7^th – 1/10^th the amount produced by men.
• The ovaries of a normal ovulatory woman secrete ~0.05-0.1 mg TESTOSTERONE/day;

During reproductive years most TESTOSTERONE produced by ovaries is converted to ESTRADIOL

Post-menopausal TESTOSTERONE production decreases gradually – to only 1/3 of premenopausal amounts (estrogen decreases more dramatically);

Removing ovaries causes TESTOSTERONE production to fall by 25% – i.e. leaving only adrenal and peripheral production;

Estrogen replacement therapy reduces TESTOSTERONE production.

TESTOSTERONE production control

• GnRH from hypothalamus stimulates pituitary secretion of Luteinizing Hormone (LH) – which stimulates secretion of TESTOSTERONE from ovaries;

Hypothalamus → GnRH → Pituitary → LH → Ovaries → TESTOSTERONE

• By negative feedback, elevated levels of TESTOSTERONE suppress the release of hypothalamic GnRH – ESTRADIOL also suppresses GnRH;

TESTOSTERONE production is also inhibited by:  the inhibition of LH output,by circulating non-SHBG-bound TESTOSTERONE, and especially by DHT (to provide negative feedback control of its own production, which is stimulated by LH); although, even in men, the major hormone involved in LH feedback is ESTRADIOL, not TESTOSTERONE; (SHBG is Sex Hormone Binding Globulin)

TESTOSTERONE is synthesized via two pathways:

• Δ4 pathway – From ANDROSTENEDIONE (via 17-βhydroxysteroid dehydrogenase enzyme) (preferred pathway)
• Δ5 pathway – From ANDROSTENEDIOL (itself synthesized from DHEA)