Publication: A microRNA switch regulates the rise in hypothalamic GnRH production before puberty.
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Identifiers
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
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Publishing Group
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.
Description
MeSH Terms
Aging
Animals
Fertility
Gonadotropin-releasing hormone
Hypogonadism
Hypothalamus
Animals
Fertility
Gonadotropin-releasing hormone
Hypogonadism
Hypothalamus
DeCS Terms
Animales
Envejecimiento
Fertilidad
Hipogonadismo
Hipotálamo
Hormona liberadora de gonadotropina
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