Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Human Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Endocrinol (Lausanne). 2022 Jun 28;13:925206. doi: 10.3389/fendo.2022.925206. eCollection 2022.
The discovery of kisspeptin as a critical central regulatory factor of GnRH release has given people a novel understanding of the neuroendocrine regulation in human reproduction. Kisspeptin activates the signaling pathway by binding to its receptor kisspeptin receptor (KISS1R) to promote GnRH secretion, thereby regulating the hypothalamic-pituitary-gonadal axis (HPG) axis. Recent studies have shown that kisspeptin neurons located in arcuate nucleus (ARC) co-express neurokinin B (NKB) and dynorphin (Dyn). Such neurons are called KNDy neurons. KNDy neurons participate in the positive and negative feedback of estrogen to GnRH secretion. In addition, kisspeptin is a key factor in the initiation of puberty, and also regulates the processes of female follicle development, oocyte maturation, and ovulation through the HPG axis. In male reproduction, kisspeptin also plays an important role, getting involved in the regulation of Leydig cells, spermatogenesis, sperm functions and reproductive behaviors. Mutations in the gene or disorders of the kisspeptin/KISS1R system may lead to clinical symptoms such as idiopathic hypogonadotropic hypogonadism (iHH), central precocious puberty (CPP) and female infertility. Understanding the influence of kisspeptin on the reproductive axis and related mechanisms will help the future application of kisspeptin in disease diagnosis and treatment. In this review, we critically appraise the role of kisspeptin in the HPG axis, including its signaling pathways, negative and positive feedback mechanisms, and its control on female and male reproduction.
作为 GnRH 释放的关键中枢调节因子， kisspeptin 的发现使人们对人类生殖的神经内分泌调节有了新的认识。 kisspeptin 通过与受体 kisspeptin 受体（KISS1R）结合激活信号通路，促进 GnRH 分泌，从而调节下丘脑-垂体-性腺轴（HPG）。最近的研究表明，位于弓状核（ARC）中的 kisspeptin 神经元共同表达神经激肽 B（NKB）和强啡肽（Dyn）。这些神经元称为 KNDy 神经元。KNDy 神经元参与雌激素对 GnRH 分泌的正反馈和负反馈。此外， kisspeptin 是青春期启动的关键因素，也通过 HPG 轴调节女性卵泡发育、卵母细胞成熟和排卵过程。在男性生殖中， kisspeptin 也起着重要作用，参与调节间质细胞、精子发生、精子功能和生殖行为。基因或 kisspeptin/KISS1R 系统的紊乱可能导致特发性低促性腺激素性性腺功能减退症（iHH）、中枢性性早熟（CPP）和女性不孕等临床症状。了解 kisspeptin 对生殖轴的影响及其相关机制将有助于 kisspeptin 在疾病诊断和治疗中的未来应用。在这篇综述中，我们批判性地评价了 kisspeptin 在 HPG 轴中的作用，包括其信号通路、正负反馈机制及其对女性和男性生殖的控制。
