| First Author | Lannes J | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 31563 | PubMed ID | 27539363 |
| Mgi Jnum | J:253795 | Mgi Id | MGI:6102356 |
| Doi | 10.1038/srep31563 | Citation | Lannes J, et al. (2016) A regulatory loop between miR-132 and miR-125b involved in gonadotrope cells desensitization to GnRH. Sci Rep 6:31563 |
| abstractText | The GnRH neurohormone is the main activator of the pituitary gonadotropins, LH and FSH. Here we investigated the contribution of microRNAs in mediating GnRH activation. We first established that miR-125b targets several actors of Galphaq/11 signalling pathway, without altering Galphas pathway. We then showed that a Galphas-mediated, PKA-dependent phosphorylation of NSun2 methyltransferase leads to miR-125b methylation and thereby induces its down-regulation. We demonstrated that NSun2 mRNA is a target of miR-132 and that NSun2 may be inactivated by the PP1alpha phosphatase. Time-course analysis of GnRH treatment revealed an initial NSun2-dependent down-regulation of miR-125b with consecutive up-regulation of LH and FSH expression. Increase of miR-132 and of the catalytic subunit of PP1alpha then contributed to NSun2 inactivation and to the return of miR-125b to its steady-state level. The Galphaq/11-dependent pathway was thus again silenced, provoking the down-regulation of LH, FSH and miR-132. Overall, this study reveals that a regulatory loop that tends to maintain or restore high and low levels of miR-125b and miR-132, respectively, is responsible for gonadotrope cells desensitization to sustained GnRH. A dysregulation of this loop might be responsible for the inverted dynamics of these two miRNAs reported in several neuronal and non-neuronal pathologies. |
