The role of kisspeptin in the control of gonadotrophin secretion

BACKGROUND: Kisspeptins, and their cognate receptor gpr-54, were first found to regulate the hypothalamic-pituitary-gonadal (HPG) axis in 2003, when two groups demonstrated that mutations in gpr-54 cause idiopathic hypogonadotropic hypogonadism characterized by delayed or absent puberty. This review aims to highlight discoveries in the KiSS-1/gpr-54 system, focusing on their regulation of the HPG axis in male and female reproductive systems of both mammalian and non-mammalian vertebrates. METHODS: A search of PUBMED and the authors' files was done without limitations by language or species for citations relevant to kisspeptin, reproduction and signal transduction. RESULTS: Kisspeptins and gpr-54 are critical for puberty and the regulation of reproduction. Kisspeptins have been implicated in mediating many of the important signals relayed to the gonadotrophin-releasing hormone (GnRH) neuron such as positive and negative feedback, metabolic input and photoperiod. The ability of kisspeptin neurons to co-ordinate different signals impinging on the HPG axis makes it one of the most important regulators of GnRH and the reproductive axis. CONCLUSIONS: Kisspeptins are pivotal regulators of the HPG axis and reproduction, with the ability to integrate signals from both internal and external sources. Knowledge about the signalling mechanisms involved in kisspeptin stimulation of GnRH would help improve the understanding of the importance of this critical pathway in reproduction.