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.

A G protein–coupled receptor mediates neuropeptide-induced oocyte maturation in the jellyfish Clytia

“…Molecular phylogeny showed that Clytia MIHR is not closely related to receptors of the core hypothalamus-pituitary-gonadal GPCRs, but rather forms a superfamily with receptors of these "upstream" neuropeptide hormones, notably GnIH, QRFP, Neuropeptide Y, and NkB. Production of GnRH and gonadotropins along the hypothalamus-pituitary-gonadal axis are inhibited by GnIH and stimulated by QRFPs [47,48], while the tachykinin family hormone NkB acts in a group of hypothalamus neurons together with kisspeptin and dynorphin A in the generation of cyclic GnRH pulses [49]. The ancestral cnidarian-bilaterian GPCR for MIHR and the receptors to all these vertebrate hormones may thus already have had a role in regulating gamete production and/or release.…”

A G-protein-coupled receptor mediates neuropeptide-induced oocyte maturation in the jellyfish Clytia

“…Molecular phylogeny showed that Clytia MIHR is not closely to receptors of the core H-P-G GPCRs, but rather forms a superfamily with receptors of these "upstream" neuropeptide hormones, notably GnIH, QRFP, Neuropeptide Y and NkB. Production of GnRH and gonadotropins along the H-P-G axis are inhibited by GnIH and stimulated by QRFPs [45,46], while the Tachykinin family hormone NkB acts in a group of hypothalamus neurons together with Kisspeptin and Dynorphin A in the generation of cyclic GnRH pulses [47]. The ancestral cnidarian-bilaterian GPCR for MIHR and the receptors to all these vertebrate hormones may thus already had a role in regulating gamete production and/or release.…”

Pathophysiology of hot flashes with focus on neurohormonal regulation (a review)

“…Kiss1-нейроны аркуатного ядра инфундибулярной области (группа КNDy-нейронов) участвуют в отрицательной обратной связи между половыми стероидами и гонадотропинами, обеспечивая тоническую секрецию ГнРГ, с участием динорфина (супрессора синтеза ГнРГ) и нейрокинина В (стимулятора синтеза ГнРГ). Они формируют аутосинаптическую петлю обратной связи и модулируют пульсативную секрецию ГнРГ и соответственно синтез ЛГ и ФСГ [30]. Kiss1-нейроны ростральной части поля III желудочка играют ключевую роль в передаче положительной обратной связи эстрадиола на гонадотропины, в первую очередь регулируя пульсативную активность гонадолиберина, в присутствии активированных рецепторов прогестерона, что инициирует преовуляторный пик ГнРГ [3,25,31] (рис.…”