Neurokinin B and reproductive functions: "KNDy neuron" model in mammals and the emerging story in fish

Abstract

In mammals, neurokinin B (NKB), the gene product of the tachykinin family member TAC3, is known to be a key regulator for episodic release of luteinizing hormone (LH). Its regulatory actions are mediated by a subpopulation of kisspeptin neurons within the arcuate nucleus with co-expression of NKB and dynorphin A (commonly called the "KNDy neurons"). By forming an "autosynaptic feedback loop" within the hypothalamus, the KNDy neurons can modulate gonadotropin-releasing hormone (GnRH) pulsatility and subsequent LH release in the pituitary. NKB regulation of LH secretion has been recently demonstrated in zebrafish, suggesting that the reproductive functions of NKB may be conserved from fish to mammals. Interestingly, the TAC3 genes in fish not only encode the mature peptide of NKB but also a novel tachykinin-like peptide, namely NKB-related peptide (or neurokinin F). Recent studies in zebrafish also reveal that the neuroanatomy of TAC3/kisspeptin system within the fish brain is quite different from that of mammals. In this article, the current ideas of "KNDy neuron" model for GnRH regulation and steroid feedback, other reproductive functions of NKB including its local actions in the gonad and placenta, the revised model of tachykinin evolution from invertebrates to vertebrates, as well as the emerging story of the two TAC3 gene products in fish, NKB and NKB-related peptide, will be reviewed with stress on the areas with interesting questions for future investigations.

Keywords: Gonadotropin-releasing hormone; KNDy neurons; Kisspeptin; Neurokinin B; Neurokinin receptor; Reproduction.