Physiological roles of the kisspeptin/GPR54 system in the neuroendocrine control of reproduction.

Reproductive maturation and function are maintained by a complex neurohormonal network that integrates at the so-called hypothalamic-pituitary-gonadal (HPG) axis. This system is hierarchically controlled by the decapeptide, GnRH, which in turn is under the dynamic regulation of multiple stimulatory and inhibitory pathways, including peripheral signals (prominently, sex steroids) and different central modulators. Among the latter, considerable interest has been raised recently by the identification of the major roles and mechanisms of action of kisspeptins, a family of neuropeptides encoded by the Kiss1 gene, which acting via the G protein-coupled receptor, GPR54, have been shown to play essential functions as potent activators and major gatekeepers of the HPG axis. Indeed, kisspeptin neurons, whose mere existence and neuroendocrine dimension had escaped from general attention up to five years ago, have been now universally recognized as key players in the control of critical aspects of reproductive development and function, from sexual differentiation to regulation of GnRH/gonadotropin secretion and the metabolic gating of fertility. In this chapter, we will provide a concise summary of the state of the art in this rapidly evolving area of neuroendocrinology, with special emphasis on recent developments and contentious issues that are likely to attract considerable attention in the coming years.