| First Author | Breen SM | Year | 2013 |
| Journal | Mol Endocrinol | Volume | 27 |
| Issue | 9 | Pages | 1483-91 |
| PubMed ID | 23836924 | Mgi Jnum | J:241984 |
| Mgi Id | MGI:5904115 | Doi | 10.1210/me.2013-1130 |
| Citation | Breen SM, et al. (2013) Ovulation involves the luteinizing hormone-dependent activation of G(q/11) in granulosa cells. Mol Endocrinol 27(9):1483-91 |
| abstractText | The LH receptor (LHR) activates several families of heterotrimeric G proteins, but only the activation of Gs and subsequent generation of cAMP are universally accepted as important mediators of LH actions. To examine the involvement of the Gq/11 family on the actions of LH, we crossed Cyp19Cre and Galphaq(f/f);Galpha11(-/-) mice to generate mice with a granulosa cell-specific deletion of Galphaq in the context of a global deletion of Galpha11. Granulosa cells from Galphaq(f/f);Galpha11(-/-);Cre(+) mice have barely detectable levels of Galphaq/11, have a normal complement of LHR, and respond to LHR activation with a transient increase in cAMP accumulation, but they fail to respond with increased inositol phosphate accumulation, an index of the activation of Galphaq/11. The LHR-provoked resumption of meiosis, cumulus expansion, and luteinization are normal. However, the Galphaq(f/f);Galpha11(-/-);Cre(+) mice display severe subfertility because many of the oocytes destined for ovulation become entrapped in preovulatory follicles or corpora lutea. Because follicular rupture is known to be dependent on the expression of the progesterone receptor (Pgr), we examined the LHR-induced expression of Pgr and 4 of its target genes (Adamts-1, Ctsl1, Edn2, and Prkg2). These actions of the LHR were impaired in the ovaries of the Galphaq(f/f);Galpha11(-/-);Cre(+) mice. We conclude that the defect in follicular rupture is secondary to the failure of the LHR to fully induce the expression of the Pgr. This is the first conclusive evidence for the physiological importance of the activation of Gq/11 by the LHR and for the involvement of Galphaq/11 in ovulation. |
