| Literature DB >> 27135215 |
Andrea Messina1,2, Fanny Langlet1,2,3, Konstantina Chachlaki1,2, Juan Roa4,5,6, Sowmyalakshmi Rasika7, Nathalie Jouy1,2, Sarah Gallet1,2, Francisco Gaytan4,5,6, Jyoti Parkash1,2, Manuel Tena-Sempere4,5,6, Paolo Giacobini1,2, Vincent Prevot1,2.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2016 PMID： 27135215 DOI： 10.1038/nn.4298
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884