Kisspeptin (KP) and neurokinin B (NKB) are neuropeptides that govern the reproductive endocrine axis through regulating hypothalamic gonadotropin-releasing hormone (GnRH) neuronal activity and pulsatile GnRH secretion. Their critical role in reproductive health was first identified after inactivating variants in genes encoding for KP or NKB signaling were shown to result in congenital hypogonadotropic hypogonadism and a failure of pubertal development. Over the past 2 decades since their discovery, a wealth of evidence from both basic and translational research has laid the foundation for potential therapeutic applications. Beyond KP's function in the hypothalamus, it is also expressed in the placenta, liver, pancreas, adipose tissue, bone, and limbic regions, giving rise to several avenues of research for use in the diagnosis and treatment of pregnancy, metabolic, liver, bone, and behavioral disorders. The role played by NKB in stimulating the hypothalamic thermoregulatory center to mediate menopausal hot flashes has led to the development of medications that antagonize its action as a novel nonsteroidal therapeutic agent for this indication. Furthermore, the ability of NKB antagonism to partially suppress (but not abolish) the reproductive endocrine axis has supported its potential use for the treatment of various reproductive disorders including polycystic ovary syndrome, uterine fibroids, and endometriosis. This review will provide a comprehensive up-to-date overview of the preclinical and clinical data that have paved the way for the development of diagnostic and therapeutic applications of KP and NKB.

中文翻译：

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Kisspeptin 和 Neurokinin B 的新兴治疗潜力。


Kisspeptin (KP) 和神经激肽 B (NKB) 是通过调节下丘脑促性腺激素释放激素 (GnRH) 神经元活动和脉冲式 GnRH 分泌来控制生殖内分泌轴的神经肽。在编码 KP 或 NKB 信号的基因失活变异被证明会导致先天性低促性腺激素性性腺功能减退症和青春期发育失败后，首次确定了它们在生殖健康中的关键作用。自发现以来的过去 20 年来，来自基础和转化研究的大量证据为潜在的治疗应用奠定了基础。除了 KP 在下丘脑中的功能外，它还在胎盘、肝脏、胰腺、脂肪组织、骨骼和边缘区域中表达，从而产生了用于妊娠、代谢、肝脏、骨骼的诊断和治疗的多种研究途径和行为障碍。 NKB 在刺激下丘脑体温调节中心介导更年期潮热方面发挥的作用，导致了拮抗其作用的药物的开发，成为治疗该适应症的新型非甾体治疗剂。此外，NKB 拮抗作用部分抑制（但不是消除）生殖内分泌轴的能力支持其潜在用于治疗各种生殖疾病，包括多囊卵巢综合征、子宫肌瘤和子宫内膜异位症。本综述将对临床前和临床数据提供全面的最新概述，这些数据为 KP 和 NKB 的诊断和治疗应用的开发铺平了道路。