G protein βγ subunits inhibit nongenomic progesterone-induced signaling and maturation in Xenopus laevis oocytes -: Evidence for a release of inhibition mechanism for cell cycle progression

Progesterone-induced maturation of Xenopus oocytes is a well known example of nongenomic signaling by steroids; however, little is known about the early signaling events involved in this process. Previous work has suggested that G proteins and G protein-coupled receptors may be involved in progesterone-mediated oocyte maturation as well as in other nongenomic steroid-induced signaling events. To investigate the role of G proteins in nongenomic signaling by progesterone, the effects of modulating G alpha and G beta gamma levels in Xenopus oocytes on progesterone-induced signaling and maturation were examined. Our results demonstrate that G beta gamma subunits, rather than G alpha, are the principal mediators of progesterone action in this system. We show that overexpression of G beta gamma inhibits both progesterone-induced maturation and activation of the MAPK pathway, whereas sequestration of endogenous G beta gamma subunits enhances: progesterone-mediated signaling and maturation. These data are consistent with a model whereby endogenous free Xenopus G beta gamma subunits constitutively inhibit oocyte maturation. Progesterone may induce maturation by antagonizing this inhibition and therefore allowing cell cycle progression to occur. These studies offer new insight into the early signaling events mediated by progesterone and may be useful in characterizing and identifying the membrane progesterone receptor in oocytes.