Abbara Ali, Dhillo Waljit S
Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, United Kingdom.
Department of Endocrinology, Imperial College Healthcare NHS Trust, London, United Kingdom.
J Clin Invest. 2024 Aug 1;134(15):e182669. doi: 10.1172/JCI182669.
Kisspeptin is an essential neuropeptide sitting at the apex of the hypothalamo-pituitary-gonadal (HPG) endocrine axis to regulate gonadotropin-releasing hormone (GnRH) neurons and downstream reproductive hormones. Kisspeptin neurons integrate feedback from sex steroids facilitating regulation of the menstrual cycle and mediate the effects of metabolic stressors on the reproductive axis. In this issue of the JCI, Torres and colleagues describe another pathway for kisspeptin signaling in astrocytes to influence GnRH neuronal output. Astrocytes had kisspeptin receptors that activated canonical intracellular signaling pathways to constrain the magnitude of kisspeptin-induced GnRH neuronal stimulation. Additionally, the appositions between kisspeptin and GnRH neurons were dynamic during the ovarian cycle, with astrocyte kisspeptin signaling proposed as a putative modulator of this neuroplasticity. Importantly, astrocyte kisspeptin signaling also mediated susceptibility to metabolic stressors and the development of obesity-induced hypogonadism, underscoring the physiological and pathological importance of this pathway and revealing the importance of nonneuronal signaling in reproductive health.
kisspeptin是一种重要的神经肽，位于下丘脑 - 垂体 - 性腺（HPG）内分泌轴的顶端，以调节促性腺激素释放激素（GnRH）神经元和下游生殖激素。Kisspeptin神经元整合来自性类固醇的反馈，促进月经周期的调节，并介导代谢应激源对生殖轴的影响。在本期《临床研究杂志》中，托雷斯及其同事描述了星形胶质细胞中kisspeptin信号传导影响GnRH神经元输出的另一条途径。星形胶质细胞具有kisspeptin受体，可激活经典的细胞内信号通路，以限制kisspeptin诱导的GnRH神经元刺激的幅度。此外，在卵巢周期中，kisspeptin与GnRH神经元之间的并置是动态的，星形胶质细胞kisspeptin信号传导被认为是这种神经可塑性的一种假定调节因子。重要的是，星形胶质细胞kisspeptin信号传导还介导了对代谢应激源的易感性以及肥胖诱导的性腺功能减退的发展，强调了该途径的生理和病理重要性，并揭示了非神经元信号传导在生殖健康中的重要性。
