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Nat Neurosci. 2016 Jun;19(6):835-44. doi: 10.1038/nn.4298. Epub 2016 May 2.

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

Author information

1
Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, U1172, Lille, France.
2
University of Lille, FHU 1,000 Days for Health, School of Medicine, Lille, France.
3
Columbia University Medical Center and Berrie Diabetes Center, New York, New York, USA.
4
Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.
5
Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC/HURS), Cordoba, Spain.
6
CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Cordoba, Spain.
7
Inserm UMR1141 - PROTECT (Promoting Research Oriented Towards Early CNS Therapies), Paris, France.

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.

Comment in

PMID:
27135215
DOI:
10.1038/nn.4298
[Indexed for MEDLINE]

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