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␣ and G␤␥ levels in Xenopus oocytes on progesterone-induced signaling and maturation were examined. Our results demonstrate that G␤␥ subunits, rather than G␣, are the principal mediators of progesterone action in this system. We show that overexpression of G␤␥ inhibits both progesterone-induced maturation and activation of the MAPK pathway, whereas sequestration of endogenous G␤␥ subunits enhances progesterone-mediated signaling and maturation. These data are consistent with a model whereby endogenous free Xenopus G␤␥ 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.Steroid hormones are traditionally known to mediate their signaling and subsequent biological activities via nuclear receptors (1). Interestingly, many steroid-induced signaling events appear to be triggered independently from the classic nuclear receptor pathways. In fact, these processes likely involve steroid signaling via membrane receptors (2). Examples of rapid, nongenomic signaling by steroids are myriad, including aldosterone-induced increases in intracellular calcium in vascular smooth muscle cells (3-8), estrogen-mediated induction of nitric-oxide synthase in vascular endothelial cells (9 -12), vitamin D-induced increases in intracellular calcium in osteosarcoma cells (13)(14)(15), and progesterone-mediated maturation of amphibian and fish oocytes (16 -18).The phenomenon of progesterone-induced maturation of Xenopus oocytes serves as a useful experimental model for studying nongenomic steroid signaling (16, 19 -21). The maturation of an oocyte refers to the meiotic stage at which an oocyte rests. "Immature" oocytes are arrested in prophase of meiosis I. Before ovulation, oocytes are induced to re-enter the cell cycle, finally resting in metaphase II. These "mature" oocytes are then competent for ovulation and subsequent fertilization, after which the final stages of meiosis are completed (16).Evidence suggests that progesterone-induced maturation of Xenopus oocytes is mediated by cell surface rather than nuclear receptors. First, maturation is unaffected by the transcriptional inhibitor actinomycin D (21). Second, progesterone covalently attached to either polymers or bovine serum albumin and therefore unable to diffuse through the oocyte mem...

Steroids can induce both transcription-dependent (genomic) and independent (nongenomic) signaling. Here, several classical androgen receptor ligands were tested for their ability to modulate genomic and nongenomic responses, focusing on the role of the oocyte-expressed Xenopus classical androgen receptor (XeAR) in mediating these processes. Cellular fractionation and immunohistochemistry revealed that the XeAR was located throughout oocytes, including within the plasma membrane. RNA interference and oocyte maturation studies suggested that androgen-induced maturation was mediated in part by the XeAR in a transcription-independent fashion, perhaps by altering G protein-mediated signaling. While inducing minimal transcription in oocytes, all AR ligands promoted significant XeAR-mediated transcription in CV1 cells. In contrast, only testosterone and androstenedione potently induced oocyte maturation, whereas dihydrotestosterone and R1881 actually inhibited testosterone and human chorionic gonadotropin-induced maturation and signaling. These results suggest that the nature of a steroid-induced signal (genomic vs. nongenomic) may depend on the type of target cell, the receptor location within cells, as well as the ligand itself. The identification of molecules capable of selectively altering genomic vs. nongenomic signaling may be useful in delineating the roles of these pathways in mediating androgen responses and might lead to the development of novel compounds that specifically modulate these signals in vivo.