| First Author | Messina A | Year | 2016 |
| Journal | Nat Neurosci | Volume | 19 |
| Issue | 6 | Pages | 835-44 |
| PubMed ID | 27135215 | Mgi Jnum | J:235013 |
| Mgi Id | MGI:5792620 | Doi | 10.1038/nn.4298 |
| Citation | Messina A, et al. (2016) A microRNA switch regulates the rise in hypothalamic GnRH production before puberty. Nat Neurosci 19(6):835-44 |
| abstractText | 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. |
