The hypothalamus-pituitary-gonad axis: Tales of mice and men

Reproduction is controlled by the hypothalamic-pituitary-gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH) neurons play a central role in this axis through production of GnRH, which binds to a membrane receptor on pituitary gonadotrophs and stimulates the biosynthesis and secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Multiple factors affect GnRH neuron migration, GnRH gene expression, GnRH pulse generator, GnRH secretion, GnRH receptor expression, and gonadotropin synthesis and release. Among them anosmin is involved in the guidance of the GnRH neuron migration, and a loss-of-function mutation in its gene leads to a failure of their migration from the olfactory placode to the hypothalamus, with consequent anosmic hypogonadotropic hypogonadism (Kallmann syndrome). There are also cases of hypogonadotropic hypogonadim with normal sense of smell, due to mutations of other genes. Another protein, kisspeptin plays a crucial role in the regulation of GnRH pulse generator and the pubertal development. GnRH is the main hypothalamic regulator of the release of gonadotropins. Finally, FSH and LH are the essential hormonal regulators of testicular functions, acting through their receptors in Sertoli and Leydig cells, respectively. The main features of the male HPG axis will be described in this review.