Mills Edouard G, Tsoutsouki Jovanna, Pierret Aureliane C S, Comninos Alexander N, Dhillo Waljit S
Section of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Department of Endocrinology, Imperial College Healthcare NHS Trust, London W6 8RF, UK.
J Clin Endocrinol Metab. 2025 May 19;110(6):e1747-e1758. doi: 10.1210/clinem/dgaf055.
Reproductive success and ultimately species survival at a population level is contingent on a plethora of neuroendocrine signals working in concert to regulate gonadal function and reproductive behavior. Among these, the neuropeptide kisspeptin (encoded by the KISS1/Kiss1 gene) has emerged as the master regulator of the hypothalamic-pituitary-gonadal axis. Besides the hypothalamus, both kisspeptin and its cognate receptor are extensively expressed throughout cortico-limbic brain structures in rodents and humans, which are regions traditionally implicated in behavioral and emotional responses. Thus, there exists a neuroanatomical framework through which kisspeptin can integrate reproductive behavior and emotional regulation with the reproductive axis. Accordingly, this sets the scene for recent findings derived from an assortment of species, including humans, unveiling kisspeptin as an important gatekeeper of reproductive behavior and emotional control. Herein, we summarize the major preclinical animal and human experimental evidence identifying kisspeptin as a key neuromodulator of reproductive behavior and emotional state. Such findings have laid the foundations for clinical applications of kisspeptin-based therapies for patients with related reproductive and psychosexual disorders.
在种群水平上,生殖成功乃至物种生存取决于众多神经内分泌信号协同作用,以调节性腺功能和生殖行为。其中,神经肽 kisspeptin(由 KISS1/Kiss1 基因编码)已成为下丘脑 - 垂体 - 性腺轴的主要调节因子。除下丘脑外,kisspeptin 及其同源受体在啮齿动物和人类的整个皮质 - 边缘脑结构中广泛表达,这些区域传统上与行为和情绪反应有关。因此,存在一个神经解剖学框架,通过该框架 kisspeptin 可以将生殖行为和情绪调节与生殖轴整合起来。相应地,这为包括人类在内的各种物种的最新研究结果奠定了基础,这些结果揭示 kisspeptin 是生殖行为和情绪控制的重要守门人。在此,我们总结了主要的临床前动物和人体实验证据,这些证据确定 kisspeptin 是生殖行为和情绪状态的关键神经调节因子。这些发现为基于 kisspeptin 的疗法在患有相关生殖和性心理障碍患者中的临床应用奠定了基础。