Messina, AndreaLanglet, FannyChachlaki, KonstantinaRoa, JuanRasika, SowmyalakshmiJouy, NathalieGallet, SarahGaytan, FranciscoParkash, JyotiTena-Sempere, ManuelGiacobini, PaoloPrevot, Vincent2023-01-252023-01-252016-04-01Messina A, Langlet F, Chachlaki K, Roa J, Rasika S, Jouy N, et al. A microRNA switch regulates the rise in hypothalamic GnRH production before puberty. Nat Neurosci. 2016 Jun;19(6):835-44. doi: 10.1038/nn.4298. Epub 2016 May 2. Erratum in: Nat Neurosci. 2016 Jul 26;19(8):1115http://hdl.handle.net/10668/10045A 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.enMice, inbred C57BLMice, transgenicMicroRNAsReproductionSexual maturationAgingAnimalsFertilityGonadotropin-releasing hormoneHypogonadismHypothalamusresearch article27135215open accessAnimalesEnvejecimientoFertilidadHipogonadismoHipotálamoHormona liberadora de gonadotropina10.1038/nn.42981546-1726https://www.hal.inserm.fr/inserm-03204447v2/file/Messina%20NatNeurosci%20Rev%20man.pdf