Testosterone and progesterone rapidly attenuate plasma membrane Gbetagamma-mediated signaling in Xenopus laevis oocytes by signaling through classical steroid receptors
| Autor: | Kristen Evaul, Stephen R. Hammes, Michelle Jamnongjit, Bala Bhagavath |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
G protein Xenopus Biology Models Biological Promegestone Xenopus laevis Endocrinology Internal medicine GTP-Binding Protein gamma Subunits Chlorocebus aethiops medicine Animals Testosterone Receptor Molecular Biology Progesterone Dose-Response Relationship Drug urogenital system Cell Membrane GTP-Binding Protein beta Subunits General Medicine biology.organism_classification Oocyte Potassium channel Androgen receptor medicine.anatomical_structure COS Cells Androgens Oocytes Signal transduction Signal Transduction |
| Zdroj: | Molecular endocrinology (Baltimore, Md.). 21(1) |
| ISSN: | 0888-8809 |
| Popis: | Many transcription-independent (nongenomic) steroid effects are regulated by G proteins. A well-established, biologically relevant example of steroid/G protein interplay is steroid-triggered oocyte maturation, or meiotic resumption, in Xenopus laevis. Oocyte maturation is proposed to occur through a release of inhibition mechanism whereby constitutive signaling by Gβγ and other G proteins maintains oocytes in meiotic arrest. Steroids (androgens in vivo, and androgens and progesterone in vitro) overcome this inhibition to promote meiotic resumption. To test this model, we used G protein-regulated inward rectifying potassium channels (GIRKs) as markers of Gβγ activity. Overexpression of GIRKs 1 and 2 in Xenopus oocytes resulted in constitutive potassium influx, corroborating the presence of basal Gβγ signaling in resting oocytes. Testosterone and progesterone rapidly reduced potassium influx, validating that steroids attenuate Gβγ activity. Interestingly, reduction of classical androgen receptor (AR) expression by RNA interference abrogated testosterone’s effects on GIRK activity at low, but not high, steroid concentrations. Accordingly, androgens bound to the Xenopus progesterone receptor (PR) at high concentrations, suggesting that, in addition to the AR, the PR might mediate G protein signaling when androgens levels are elevated. In contrast, progesterone bound with high affinity to both the Xenopus PR and AR, indicating that progesterone might signal and promote maturation through both receptors, regardless of its concentration. In sum, these studies introduce a novel method for detecting nongenomic steroid effects on G proteins in live cells in real time, and demonstrate that cross talk may occur between steroids and their receptors during Xenopus oocyte maturation. |
| Databáze: | OpenAIRE |
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