近日，
该团队发现下丘脑小胶质细胞通过核因子κβ (Rank)信号受体激活剂控制HPG轴。全身和小胶质细胞Rank缺失导致促性腺激素释放激素（GnRH）神经元功能改变导致促性腺功能低下（HH）。此外，课题组研究人员在HH患者中发现了罕见的RANK基因变异。Rank缺失后的转录谱显示小胶质细胞激活缺陷和中隆起的形态学改变，减少GnRH末端突起的接触和吞噬，损害GnRH神经元对kisspeptin的反应。总的来说，他们的数据揭示了小胶质细胞通过Rank信号调节GnRH神经元功能，对生殖成熟和生育有潜在的影响。
据介绍，下丘脑-垂体-性腺轴（HPG）控制青春期发育、性成熟和生育能力。
附：英文原文
Title: Microglia Rank signaling regulates GnRH neuronal function and the hypothalamic-pituitary-gonadal axis
Author: Alejandro Collado-Sole, Nozha Borjini, Jing Zhai, Francisco Ruiz-Pino, Gonzalo Soria-Alcaide, Cintia Folgueira, Celia García-Vilela, Beatriz Romero-de la Rosa, Victor Lopez, Yassine Zouaghi, An Jacobs, Bella Mora-Romero, Alexandra Barranco, Guillermo Yoldi, Karine Rizzoti, Guadalupe Sabio, Gema Perez-Chacon, Patricia G. Santamaria, Jose Antonio Esteban, Nathalie Journiac, Vincent Prevot, Alberto Pascual, Rafael Fernández-Chacón, Manuel Tena-Sempere, Nelly Pitteloud, Eva Gonzalez-Suarez
Issue&Volume: 2026-03-12
Abstract: The hypothalamic-pituitary-gonadal axis (HPG) controls pubertal development, sexual maturation, and fertility. We identified a role of hypothalamic microglia in controlling the HPG axis through receptor activator of nuclear factor κβ (Rank) signaling. Whole-body and microglia Rank depletion led to hypogonadotropic hypogonadism (HH) resulting from an alteration in gonadotropin-releasing hormone (GnRH) neuron function. In addition, we identified rare gene variants of RANK in patients with HH. Transcriptional profiling upon Rank loss revealed defective microglia activation and morphological alterations in the median eminence, decreasing the contacts and engulfment of GnRH terminal projections and impairing GnRH neuronal responses to kisspeptin. Overall, our data uncover the microglia as regulator of GnRH neuronal function through Rank signaling, with potential implications for reproductive maturation and fertility.
DOI: aeb6999
Source: https://www.science.org/doi/10.1126/science.aeb6999