Endocrine Abstracts

Puberty is a tightly regulated process through which an individual attains reproductive capability. An intricate network of central and peripheral factors play a role in this process; however, the cellular and molecular events that initiate and sustain adult reproductive function remain largely unknown. Recently, kisspeptin (encoded by Kiss1) and neurokinin B (NKB, encoded by TAC3 in humans and Tac2 in rodents) have been shown to be gate-keepers of puberty onset. Studies in humans and rodents have shown loss-of-function mutations in either Kiss1/NKB or their receptors, Kiss1r/NK3R, produce congenital hypogonadotropic hypogonadism and infertility, but beyond these observations and correlations that link sexual development to changes in Kiss1 and NKB expression, we have little understanding of precisely how NKB and kisspeptin guide pubertal maturation. We and others have shown that kisspeptin, NKB and dynorphin A (Dyn) are co-expressed in neurons of the arcuate nucleus; moreover, these neurons also co-express NK3R. NKB has been shown to stimulate LH release, presumably by acting autosynaptically on these Kiss1/NKB/Dyn neurons to induce kisspeptin-mediated GnRH secretion. We have proposed a model in which NKB works in concert with the counter-regulatory action of dyn (acting through interneurons) to shape the coordinated ultradian release of kisspeptin and GnRH and thereby drive the pulsatile release of LH secretion that is essential for the onset of puberty and for the maintenance of reproductive function in the adult.