Messina, AndreaLanglet, FannyChachlaki, KonstantinaRoa, JuanRasika, SowmyalakshmiJouy, NathalieGallet, SarahGaytan, FranciscoParkash, JyotiTena-Sempere, ManuelGiacobini, PaoloPrevot, VincentMessina, A.Langlet, F.Chachlaki, K.Roa, J.Rasika, S.Jouy, N.Gallet, S.Gaytan, F.Parkash, J.Tena-Sempere, M.Giacobini, P.Prevot, V.2018-01-052024-08-132018-01-052024-08-132016Messina, A., Langlet, F., Chachlaki, K., Roa, J., Rasika, S., Jouy, N., . . . Prevot, V. (2016). A microRNA switch regulates the rise in hypothalamic GnRH production before puberty. Nature Neuroscience, 19(6), 835-844. doi: 10.1038/nn.42981097625610.1038/nn.4298https://kr.cup.edu.in/handle/32116/501A 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. ? 2016 Nature Publishing Group. All rights reserved.enGonadorelinMicrornaAgingAnimalC57Bl MouseFertilityGeneticsHypogonadismHypothalamusMetabolismPhysiologyReproductionSexual MaturationTransgenic MouseAgingAnimalsFertilityGonadotropin-Releasing HormoneHypogonadismHypothalamusMice, Inbred C57BlMice, TransgenicMicrornasReproductionSexual MaturationArticlehttps://www.nature.com/articles/nn.4298