To stimulate testosterone
production, the hypothalamus releases a substance to the pituitary gland called gonadotropin-releasing hormone (GnRH). This hormone, in turn, causes the gland to produce two other hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), collectively known as gonadotropins.
LH is released into the bloodstream where it travels to the Leydig cells in the testes and stimulates testosterone biosynthesis from cholesterol. LH follows the pulsatile secretion profile of GnRH very closely, whereas FSH does not display such clear pulsatility owing to its longer half-life.
Testosterone exerts a direct, and after metabolism to estrogens an indirect, negative feedback effect on the secretion of GnRH and gonadotropins. Accordingly, plasma LH and FSH levels decrease after testosterone or estradiol administration and rise when negative feedback is disrupted by castration.
There are both similarities and differences in how FSH secretion is regulated when compared to LH. FSH binds to receptors in the Sertoli cells and promotes spermatogenesis. In addition to a number of other proteins, the hormones inhibin and activin are formed in the Sertoli cells under the influence of FSH. Inhibin is an important component in the feedback system controlling FSH secretion.
The role of FSH in spermatogenesis is, however, a matter for controversy. The classical view was that FSH stimulates spermatogenesis and that LH stimulated testosterone production. However, spermatogenesis is qualitatively maintained by testosterone alone in hypophysectomised rats or in rats immunized against GnRH. More recently, men with an inactivating mutation of the FSH receptor gene were identified in Finland. The testes of the five homozygous men were reduced in size and the sperm count and/or motility was reduced but two men were fertile implying that FSH is not essential for male fertility. On the other hand, spermatogenesis is not quantitatively normal in these models and FSH acts synergistically with testosterone in rodents or with hCG
(LH) in men implying a role for FSH receptor activation in spermatogenesis.