A microRNA switch regulates the rise in hypothalamic GnRH production before puberty - PubMed (original) (raw)

doi: 10.1038/nn.4298. Epub 2016 May 2.

Fanny Langlet 1 2 3, Konstantina Chachlaki 1 2, Juan Roa 4 5 6, Sowmyalakshmi Rasika 7, Nathalie Jouy 1 2, Sarah Gallet 1 2, Francisco Gaytan 4 5 6, Jyoti Parkash 1 2, Manuel Tena-Sempere 4 5 6, Paolo Giacobini 1 2, Vincent Prevot 1 2

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

Andrea Messina et al. Nat Neurosci. 2016 Jun.

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Abstract

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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