The hypothalamic pituitary testicular axis (HPTA) is a dynamic feedback loop. Homeostasis is the process by which an organism maintains constant internal conditions in the face of a varying external environment. The HPTA is the homeostatic system responsible for maintaining, supporting, and ensuring reproduction, bone density, muscle mass, and other important and vital physiological and psychological processes.

Structural components of the HPTA are the hypothalamo-pituitary, testicles, and androgen receptor (AR) located on certain end organs (prostate, bone, and muscle). The major hormones of the hypothalamic pituitary testicular axis are gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin, testosterone, dihydrotestosterone (DHT), and estradiol. The medical and scientific literature demonstrates interdependent communication must be at a certain functional level between the hypothalamo-pituitary, testes, and androgen receptor (AR) to maintain HPTA homeostasis.

The HPTA has two components, both spermatogenesis and testosterone production. They are not equivalent and, in fact, have two very separate hormonal processes for homeostasis. Absent FSH, there is no testicular spermatozoa production. Absent LH, there is no testicular testosterone production.

In males, luteinizing hormone (LH) secretion by the pituitary positively stimulates testicular testosterone (T) production. The pulsatile secretion of gonadotropin releasing hormone (GnRH) from the hypothalamus stimulates LH secretion. Regulation of the secretion of GnRH and LH is by the negative feedback of testosterone and estradiol at the level of the hypothalamo-pituitary. Estradiol has a much larger, inhibitory effect than testosterone, being 200-fold more effective in suppressing LH secretion. 5?-reduction, DHT, does not appear to play a significant role in the negative feedback effect.

The regulation of the feedback of luteinizing hormone (LH) in men is, in part, under the control of estrogen and requires an adequate amount of estradiol that comes from the aromatization of testosterone. The biosynthesis of estrogens from C19 steroids is catalyzed by the aromatase cytochrome P450, CYP19. This enzyme converts androstenedione and testosterone to estrone and estradiol, respectively.

Estrogens contribute substantially to the negative feedback regulation of gonadotropin secretion. A great part, if not all, of the inhibitory effect on gonadotropin secretion is mediated by the endogenous conversion of testosterone to estradiol. The restraining action of estrogens on gonadotropin secretion in men is exerted both at the pituitary and at the hypothalamic levels.