Figure 3 - Neuroendocrine control of pituitary and gonadal function.

The hypothalamus, which has a number of nuclei and pathways that affect reproductive behavior, secretes a key decapeptide, GnRH, that binds to its receptor, GnRHR, on the gonadotropes and is involved in induction of sexual maturity through its regulation of the synthesis and secretion of the pituitary gonadotropins FSH and LH. Kisspeptin (KISS1), secreted from neurons whose cell bodies are located in the anteroventral periventricular (AVPV) and arcuate (ARC) nuclei of the hypothalamus, signals through its receptor (KISSR1) to regulate pulsatile secretion of GnRH from additional hypothalamic neurons and thus affects the pathway at a higher level. FSH and LH have key roles on the gonads in both sexes, being involved in folliculogenesis, ovulation and steroidogenesis in females while functioning in gonadal growth, steroidogenesis and spermatogenesis in males. During pregnancy, human chorionic gonadotropin (hCG) production from the early placenta takes over the role of LH, stimulating the ovarian corpus luteum to produce progesterone, which, in turn, stimulates the uterus and maintains pregnancy. Equally important are a number of peptide (for example, inhibin (INH)) and steroidogenic (that is, estradiol and testosterone) feedback systems from the gonads to the pituitary and hypothalamus. Multiple mutations in this axis have been identified in humans and mice (Supplementary Tables 1 and 2).