Groupe Avenir « Génétique et Physiologie de l’initiation de la puberté » Inserm U690, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris
The regulation of the reproductive function is complex. It notably depends on highly conserved hypothalamic neuronal networks which lead to the regulation of LH and FSH synthesis and secretion by GnRH. The mechanisms of the hypothalamic regulation of the gonadotropic axis remained poorly understood until 2003 and the description of the role of kisspeptins and their receptor GPR54 as major regulators of hypothalamic GnRH secretion. The Kisspeptins/GPR54 system is the integrative center of all hormonal, metabolic and circadian afferences that converge to the gonadotropic axis during fetal life, puberty and adulthood. Description of the mechanisms underlying pubertal initiation and LH preovulatory peak can now be considered and new pharmacological targets have appeared. The description of kisspeptins role in reproduction is a very strong example of how important the analysis of rare orphan diseases can be in order to identify novel physiological systems.