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

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Date

2016-04-01

Authors

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

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Nature Publishing Group
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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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MeSH Terms

Aging
Animals
Fertility
Gonadotropin-releasing hormone
Hypogonadism
Hypothalamus

DeCS Terms

Animales
Envejecimiento
Fertilidad
Hipogonadismo
Hipotálamo
Hormona liberadora de gonadotropina

CIE Terms

Keywords

Mice, inbred C57BL, Mice, transgenic, MicroRNAs, Reproduction, Sexual maturation

Citation

Messina A, Langlet F, Chachlaki K, Roa J, Rasika S, Jouy N, et al. A microRNA switch regulates the rise in hypothalamic GnRH production before puberty. Nat Neurosci. 2016 Jun;19(6):835-44. doi: 10.1038/nn.4298. Epub 2016 May 2. Erratum in: Nat Neurosci. 2016 Jul 26;19(8):1115