%0 Journal Article
%A Messina, Andrea
%A Langlet, Fanny
%A Chachlaki, Konstantina
%A Roa, Juan
%A Rasika, Sowmyalakshmi
%A Jouy, Nathalie
%A Gallet, Sarah
%A Gaytan, Francisco
%A Parkash, Jyoti
%A Tena-Sempere, Manuel
%A Giacobini, Paolo
%A Prevot, Vincent
%T A microRNA switch regulates the rise in hypothalamic GnRH production before puberty.
%D 2016
%U http://hdl.handle.net/10668/10045
%X 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.
%K Mice, inbred C57BL
%K Mice, transgenic
%K MicroRNAs
%K Reproduction
%K Sexual maturation
%~