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

Details

Serval ID
serval:BIB_D2DE5F6E4CC3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A microRNA switch regulates the rise in hypothalamic GnRH production before puberty.
Journal
Nature Neuroscience
Author(s)
Messina A., Langlet F., Chachlaki K., Roa J., Rasika S., Jouy N., Gallet S., Gaytan F., Parkash J., Tena-Sempere M., Giacobini P., Prevot V.
ISSN
1546-1726 (Electronic)
ISSN-L
1097-6256
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
19
Number
6
Pages
835-844
Language
english
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.
Pubmed
Web of science
Create date
26/06/2016 14:37
Last modification date
21/10/2020 5:28
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