Kisspepeptin-GPR54 signaling in the neuroendocrine reproductive axis

Kisspeptins, which are products of the Kiss1 gene, and their receptor, GPR54, have emerged as key players in the regulation of gonadotropin-releasing hormone (GnRH) secretion. Mutations or targeted deletions of GPR54 produce isolated hypogonadotropic hypogonadism in humans and mice, indicating that signaling through this receptor is a prerequisite for sexual maturation. Centrally administered kisspeptins stimulate GnRH and gonadotropin secretion in prepubertal and adult animals. Kisspeptin-expressing neurons are direct targets for the negative and positive feedback actions of sex steroids, which differentially regulate the expression of KiSS-1 mRNA in various regions of the forebrain. This review highlights what is currently known about kisspeptin-GPR54 signaling in the regulation of the neuroendocrine reproductive axis.