Role of KNDy Neurons Expressing Kisspeptin, Neurokinin B, and Dynorphin A as a GnRH Pulse Generator Controlling Mammalian Reproduction

Abstract

Increasing evidence accumulated during the past two decades has demonstrated that the then-novel kisspeptin, which was discovered in 2001, the known neuropeptides neurokinin B and dynorphin A, which were discovered in 1983 and 1979, respectively, and their G-protein-coupled receptors, serve as key molecules that control reproduction in mammals. The present review provides a brief historical background and a summary of our recent understanding of the roles of hypothalamic neurons expressing kisspeptin, neurokinin B, and dynorphin A, referred to as KNDy neurons, in the central mechanism underlying gonadotropin-releasing hormone (GnRH) pulse generation and subsequent tonic gonadotropin release that controls mammalian reproduction.

Neuroendocrine control of gonadotropin‐releasing hormone: Pulsatile and surge modes of secretion

“…An important feature of the arcuate kisspeptin neurons is that they co-express many different neurotransmitters with glutamate, NKB and dynorphin A receiving most attention although several other neuropeptides are expressed in a species-specific manner. [73][74][75] The robust expression of NKB and dynorphin A in almost all arcuate kisspeptin neurons in laboratory animals has led to the useful moniker of "KNDy neurons" for this population. 48 Furthermore, the realization that KNDy neurons expressed transcripts for neurokinin 3 receptor F I G U R E 1 Schematic illustrating the role of kisspeptin neurons in the control of pulsatile and surge secretion of gonadotropin-releasing hormone (GnRH) in mice and rats.…”

“…An important feature of the arcuate kisspeptin neurons is that they co‐express many different neurotransmitters with glutamate, NKB and dynorphin A receiving most attention although several other neuropeptides are expressed in a species‐specific manner 73–75 . The robust expression of NKB and dynorphin A in almost all arcuate kisspeptin neurons in laboratory animals has led to the useful moniker of “KNDy neurons” for this population 48 .…”

Effects of aqueous extract of Albizia glaberrima on the reproductive system of female adult Wistar albino rats

“…At the doses of 200 and 400 mg/kg b.w, AEAG induced a slight non-significant increase of the relative wet weight of the ovaries and the histological examination showed the presence of Graffian follicle and newly formed corpora lutea in 60% of rats unlike that of 80% control rats which exhibited degenerated corpora lutea. In mammals, estrogen can exert a positive feedback effect on the brain by stimulating GnRH surge which induces preovulatory pituitary gonadotropins LH and FSH surge at the end of a follicular phase or proestrus phase, and this action induces ovulation that occurs in the estrous phase (Herbison, 2008;Radovick et al, 2012;Uenoyama et al, 2021). The effects of AEAG should be explained by the presence in this extract of phytoestrogens or estrogen-like substances which acted as endogenous estrogen by a positive feedback on the hypothalamic-pituitary complex or by potentializing its effect as it has been demonstrated by Zougrou et al (2018) with the aqueous extract of (Connaraceae) and by Bleu et al Cnestis ferruginea (2012b) with the aqueous extract of .…”

Aberrant Notch Signaling Pathway as a Potential Mechanism of Central Precocious Puberty

“…A large subset of the ARC neurons, excluding the AVPV KISS1 neuronal population, produce the neuromodulators NKB and Dyn [ 20 ]. Loss-of-function mutations in the tachykinin 3 (TAC3) gene, which encodes the stimulatory neuromodulator NKB, and tachykinin receptor 3 (TACR3), which encodes the NKB receptor, are associated with the development of hypogonadism and delayed puberty.…”