神经激肽B
吻素
强啡肽
弧(几何)
弓状核
人口
内分泌学
内科学
下丘脑
促性腺激素释放激素
生物
神经科学
神经肽
医学
激素
促黄体激素
受体
阿片肽
P物质
几何学
数学
环境卫生
类阿片
作者
Aleisha M. Moore,Avrey Novak,Michael N. Lehman
标识
DOI:10.1210/endocr/bqad194
摘要
Abstract There is considerable evidence that synchronized activity within a reciprocally connected population of cells in the arcuate nucleus (ARC) co-expressing kisspeptin, neurokinin B (NKB) and dynorphin (KNDy cells) is crucial for the generation of gonadotrophin-releasing hormone (GnRH) pulses in mammals. The initial “KNDy hypothesis” proposed that pulsatile GnRH secretion is elicited by episodic kisspeptin release from KNDy cells following synchronized activation and termination of the population by NKB and dynorphin, respectively. Since then, the role of KNDy cells as a critical component of the pulse generator has been further supported by studies at the single-cell level, demonstrating that the population is both necessary and sufficient for pulsatility. In addition, there have been significant modifications and expansion of the original hypothesis, including work demonstrating the critical role of glutamate in synchronization of the KNDy cell network, functional interactions with other ARC subpopulations, and the existence of species differences in the role of dynorphin in pulse generation. Here we review these recent changes and discuss how the translation of these findings has led to the development of new therapies for disorders related to pulse generation. We also outline critical gaps in knowledge that are currently limiting the application of KNDy research in the clinic, particularly regarding the role of dynorphin in pulse generation in primates.
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