Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S 1172, F-59000, Lille, France; FHU, 1000 Days for Health, F-59000, Lille, France.
Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S 1172, F-59000, Lille, France; FHU, 1000 Days for Health, F-59000, Lille, France; University Research Institute of Child Health and Precision Medicine, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Athens, Greece.
Mol Cell Endocrinol. 2021 Jul 15;532:111302. doi: 10.1016/j.mce.2021.111302. Epub 2021 May 5.
Gonadotropin-releasing hormone (GnRH) is the master regulator of the hypothalamic-pituitary-gonadal (HPG) axis, and therefore of fertility and reproduction. The release pattern of GnRH by the hypothalamus includes both pulses and surges. However, despite a considerable body of evidence in support of a determinant role for kisspeptin, the mechanisms regulating a GnRH pulse and surge remain a topic of debate. In this review we challenge the view of kisspeptin as an absolute "monarch", and instead present the idea of a Kisspeptin-nNOS-GnRH or "KiNG" network that is responsible for generating the "GnRH pulse" and "GnRH surge". In particular, the neuromodulator nitric oxide (NO) has opposite effects to kisspeptin on GnRH secretion in many respects, acting as the Yin to kisspeptin's Yang and creating a dynamic system in which kisspeptin provides the "ON" signal, promoting GnRH release, while NO mediates the "OFF" signal, acting as a tonic brake on GnRH secretion. This interplay between an activator and an inhibitor, which is in turn fine-tuned by the gonadal steroid environment, thus leads to the generation of GnRH pulses and surges and is crucial for the proper development and function of the reproductive axis.
促性腺激素释放激素（GnRH）是下丘脑-垂体-性腺（HPG）轴的主要调节剂，因此也是生育和生殖的主要调节剂。下丘脑释放 GnRH 的模式包括脉冲和激增。然而，尽管有大量证据支持 kisspeptin 具有决定性作用，但调节 GnRH 脉冲和激增的机制仍然存在争议。在这篇综述中，我们挑战了 kisspeptin 作为绝对“君主”的观点，而是提出了 Kisspeptin-nNOS-GnRH 或“KiNG”网络的概念，该网络负责产生“ GnRH 脉冲”和“ GnRH 激增”。特别是，神经调节剂一氧化氮（NO）在许多方面对 GnRH 分泌的作用与 kisspeptin 相反，它充当 kisspeptin 的 Yin，形成一个动态系统，其中 kisspeptin 提供“ON”信号，促进 GnRH 释放，而 NO 介导“OFF”信号，对 GnRH 分泌起到紧张性制动作用。这种激活剂和抑制剂之间的相互作用，反过来又受到性腺类固醇环境的精细调节，从而导致 GnRH 脉冲和激增的产生，这对于生殖轴的正常发育和功能至关重要。
