促性腺激素减退症
促性腺激素释放激素
内分泌学
生物
内科学
小RNA
人口
抑制因子
青春期延迟
神经科学
下丘脑
细胞生物学
作者
Andrea Messina,Fanny Langlet,Konstantina Chachlaki,Juan Carlos Roa,Sowmyalakshmi Rasika,Nathalie Jouy,Sarah Gallet,Francisco Gaytan,Jyoti Parkash,Manuel Tena-Sempere,Paolo Giacobini,Vincent Prevot
摘要
A sparse population of a few hundred primarily hypothalamic neurons forms the hub of a complex neuroglial network that controls reproduction in mammals by secreting the 'master molecule' gonadotropin-releasing hormone (GnRH). Timely postnatal changes in GnRH expression are essential for puberty and adult fertility. Here we report that a multilayered microRNA-operated switch with built-in feedback governs increased GnRH expression during the infantile-to-juvenile transition and that impairing microRNA synthesis in GnRH neurons leads to hypogonadotropic hypogonadism and infertility in mice. Two essential components of this switch, miR-200 and miR-155, respectively regulate Zeb1, a repressor of Gnrh transcriptional activators and Gnrh itself, and Cebpb, a nitric oxide-mediated repressor of Gnrh that acts both directly and through Zeb1, in GnRH neurons. This alteration in the delicate balance between inductive and repressive signals induces the normal GnRH-fuelled run-up to correct puberty initiation, and interfering with this process disrupts the neuroendocrine control of reproduction.
科研通智能强力驱动
Strongly Powered by AbleSci AI