RT Journal Article
T1 A microRNA switch regulates the rise in hypothalamic GnRH production before puberty.
A1 Messina, Andrea
A1 Langlet, Fanny
A1 Chachlaki, Konstantina
A1 Roa, Juan
A1 Rasika, Sowmyalakshmi
A1 Jouy, Nathalie
A1 Gallet, Sarah
A1 Gaytan, Francisco
A1 Parkash, Jyoti
A1 Tena-Sempere, Manuel
A1 Giacobini, Paolo
A1 Prevot, Vincent
K1 Mice, inbred C57BL
K1 Mice, transgenic
K1 MicroRNAs
K1 Reproduction
K1 Sexual maturation
AB 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.
PB Nature Publishing Group
YR 2016
FD 2016-04-01
LK http://hdl.handle.net/10668/10045
UL http://hdl.handle.net/10668/10045
LA en
NO Messina 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):1115
NO This research was supported by the FRM (Equipe FRM 2005 and DEQ20130326524, France to V.P.), grant BFI2011-025021 from the Spanish Ministry of Economy and Science (M.T.-S.), the ERC COST action BM1015 (V.P., P.G. and M.T.-S.) and the Fondation Bettencourt Schueller (F.L.).
DS RISalud
RD Apr 5, 2025