Endocrine Abstracts

Puberty is a tightly regulated process by which an individual attains reproductive capability. An intricate network of central and peripheral factors has been described to play a role in this process; however, the mechanism triggering puberty onset remains largely unknown. Recently, the neuropeptides kisspeptin (encoded by Kiss1) and Neurokinin B-NKB- (encoded by TAC3 in humans and Tac2 in rodents) have been placed as essential gatekeepers of puberty onset. Studies in humans and rodents have revealed that loss-of-function mutations in the genes encoding either Kiss1/NKB or their receptors, Kiss1r/neurokinin 3 receptor (NK3R), lead to the absence of sexual maturation and infertility. Kisspeptin, NKB and dynorphin A are co-expressed in neurons of the arcuate nucleus (Arc), so called KNDy neurons. Importantly, these neurons also co-express NK3R. Compelling evidence suggests a stimulatory role of NKB (or the NK3R agonist senktide) on LH release in a number of species and exogenous administration of senktide is able to rescue puberty onset in undernourished female rats. This effect is likely mediated by autosynaptic inputs of NKB on KNDy neurons to induce the secretion of GnRH in a kisspeptin-dependent manner with the coordinated action of other neuroendocrine factors such as dynorphin, glutamate or GABA. Thus, we have proposed a model in which NKB feeds back to the kiss1 neuron to shape the pulsatile release of kisspeptin, and hence GnRH, in a mechanism also dependent on the sex steroid level. Investigating how the GnRH pulse generator activates during puberty onset and remains functional in adulthood is a primary goal in recent neuroendocrinology of reproduction.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.