Overview of the impact of kisspeptin on reproductive function

Since 2003, kisspeptin and its receptor (KISS1R, also called GPR54) are recognized as major actors of the gonadotrope axis. Mutations of genes encoding the peptide or the receptor have been identified in patients with precocious puberty or hypogonadotropic hypogonadism. They are strong stimulators of GnRH neurons and are involved in various mechanisms regulating gonadotrope axis as puberty induction or positive and negative feedback regulation on the gonadotrope axis by gonadal steroids. They also mediated some metabolic or environmental signals on the reproduction axis. Kisspeptins are synthesized and secreted by hypothalamic nuclei located in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). This system is complex because neurons located in the ARC coexpress many neuromediators such as neurokinin B and dynorphin, involved in the control of gonadotrope axis. During pregnancy, kisspeptins are also secreted by placenta and should be involved in trophoblastic invasion. After kisspeptin administration to male and female animals as well as to women with hypothalamic secondary amenorrhoea, they are able to stimulate GnRH and gonadotrophin secretion. Then, kisspeptin agonists appear as valuable new tools in treatment for reproduction troubles. The aim of this review is to clarify the role of kisspeptins in regulating gonadotrophin secretion and explores their possible therapeutic use.