[Lotus]

Gonadotrophins and testicular function

FSH and LH are important regulators of spermatogenesis and steroidogenesis, acting respectively on the Sertoli cells and Leydig cells. They increase intracellular concentrations of free cholesterol and its transport through the mitochondrial membrane by the StAR protein (the regulation of StAR is the rate-limiting step in gonadotrophin-induced steroid synthesis). Here cholesterol is converted into pregnenolone, then in androstenedione, DHEA and testosterone: these androgens bind to an androgen-binding protein (ABP), which carries them in the testicular fluid. Some testosterone is converted to estradiol by Sertoli cell-derived aromatase enzyme.



Leydig cell steroidogenesis is controlled primarily by LH with negative feedback of testosterone on the hypothalamic-pituitary axis. Testosterone and FSH act synergically on the Sertoli cells, that produces inhibin (which has a selective negative feedback action on FSH secretion) and androgen receptors. The small amount of estrogen formed from peripheral aromatization of testosterone can inhibit both FSH and LH secretion.
If testicular androgen production is inhibited by the administration of exogenous androgens then spermatogenesis ceases.

Transport, metabolism and actions of androgens

The 98% of circulating testosterone is bound to albumin or to sex-hormone-binding globulin (SHBG). SHBG is synthesized in the liver and its circulating concentration is increased by estrogen or excess thyroid hormones and decreased by exogenous androgens, glucocorticoids or growth hormone and by hypothyroidism, acromegaly and obesity. In the liver, testosterone is converted to androsterone and etiocholanolone.
In target tissues, testosterone or its reduced form DHT induces release of a heat shock protein, dimerization of two receptors and translocation to the nucleus where the dimer binds to an estrogen-like hormone response element on DNA.