Integration of the hypothalamus, pituitary and testis is of critical importance to reproductive function. The hypothalamus comprises the lateral walls of the lower part of the third ventricle of the brain. The pituitary, an endocrine gland connected to the hypothalamus at the base of the brain ,is divided into two major parts: the neurohypophysis (or posterior lobe), and the adenohypophysis (or anterior lobe).The neurohypophysis, which is composed of the median eminence, infundibular stem and infundibular process, receives neural input from the brain. In contrast, the adenohypophysis, composed of the pars tuberalis, pars intermedia and pars distalis, is glandular tissue and, thus, must be regulated by factors delivered via the circulation.


Some of the neurosecretory neurons from the hypothalamus send their axons down the neural stalk to terminate in the neurohypophysis. When stimulated to depolarize, these neurons release the hormones vasopressin (also called antidiuretic hormone) and oxytocin from secretory granules into the bloodstream. Oxytocin causes contraction of smooth muscle, including that in the male reproductive tract, and vasopressin acts in the kidneys to cause water retention. In contrast to the neurohypophysis, the adenohypophysis is regulated by peptides and monoamines that are synthesized and secreted by specific hypothalamic neurons whose axons end, not in the adenohypophysis, but in the median eminence near the infundibular stem .These hormones (hypophysiotropic hormones) are transported by the portal blood system of the pituitary from the median eminence to the adenohypophysis where they stimulate the synthesis and secretion of the adenohypophysial hormones.


There are three general classes of adenohypophysical hormones synthesized and secreted by the pars distalis of the adenohypophysis: glycoprotein hormones, corticotropin-related peptides and somatomammotropin hormones. The glycoprotein hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), have well established effects on the testis; LH stimulates the secretion of testosterone by the Leydig cells, and FSH acts on the seminiferous tubules to promote spermatogenesis. The synthesis and secretion of LH and FSH are regulated, in part, by a decapeptide from the hypothalamus, gonadotropin-releasing hormone (GnRH). When administered to humans or to laboratory mammals, GnRH causes LH, and to a lesser extent FSH, to be secreted into the blood. Based on the known structure of GnRH, a number of analogs have been synthesized, some of which are far more potent than natural GnRH and are able to increase LH and FSH secretion when administered. GnRH antagonists or antisera block the effects of endogenous GnRH thereby reducing gonadotropin levels.

LH is secreted in distinct, short-term pulses in response to pulsatile release of GnRH .The importance of pulsatile secretion of GnRH is clearly illustrated by the effect of intermittent versus continuous GnRH administration on the secretion of LH and FSH in GnRH-deficient hypogonadal men; LH and FSH can be restored to normal levels in the serum when GnRH is administered intermittently, but not when it is administered continuously. Indeed, sustained hormonal signals can shut down, rather than stimulate, target cells.The episodic LH signals that are delivered to the testis via the testicular vascular system stimulate the synthesis and secretion of testosterone by Leydig cells. As is the case for LH, testosterone is secreted in pulses .Simple, one-to-one, relationships between LH pulses from the adenohypophysis and testosterone pulses from the Leydig cell are often seen, although there are reports that LH pulses are not necessarily followed or preceded by a testosterone pulse. Interestingly, maximal steroidogenesis occurs at concentrations of LH that are sufficient to occupy only a small fraction of the total number of LH receptors available on the surface of Leydig cells. The significance of this relative overabundance of receptors is unclear. Fig. 3 shows testosterone production during the lifetime of the human male. Peaks of testosterone occur in the peripheral blood of the 12-18 week-old fetus, and of the 2 month-old neonate. In the prepubertal period, testosterone declines to low levels. It then increases markedly during puberty (ages 12 to 17 years), and reaches its maximum during the second and third decades of adult life. Slow decline then occurs through the fifth decade, with more dramatic decline thereafter. Superimposed on these episodes are annual, daily and hourly fluctuations in testosterone production.