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A microRNA switch regulates the rise in hypothalamic GnRH production before puberty
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Journal Article
A microRNA switch regulates the rise in hypothalamic GnRH production before puberty
2016
Overview
The authors show that a gene expression switch operated by microRNAs regulates the control of puberty onset and adult fertility by the CNS by triggering increased hypothalamic
Gnrh
mRNA expression during the infantile period of postnatal development.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 45
/ 45/91
/ 64
/ 82
/ Aging
/ Animal Genetics and Genomics
/ Animals
/ Brain
/ Diabetes
/ Females
/ Genes
/ Gonadotropin releasing hormone
/ Gonadotropin-Releasing Hormone - genetics
/ Gonadotropin-Releasing Hormone - metabolism
/ Hormones
/ Males
/ MicroRNA
/ Neurons
/ Puberty
/ RNA
/ Sexual Maturation - physiology
/ Vagina
