A microRNA switch regulates the rise in hypothalamic GnRH production before puberty

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Messina, Andrea | Langlet, Fanny | Chachlaki, Konstantina | Roa, Juan | Rasika, Sowmyalakshmi | Jouy, Nathalie | Gallet, Sarah | Gaytan, Francisco | Parkash, Jyoti | Tena-Sempere, Manuel | Giacobini, Paolo | Prevot, Vincent

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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