Depletion of calcium stores contributes to progesterone-induced attenuation of calcium signaling of G protein-coupled receptors.
Progesterone non-genomically attenuates the calcium signaling of the human oxytocin receptor and several other Galpha(q) protein-coupled receptors. High progesterone concentrations are found in the endometrium during pregnancy opposing the responsiveness of the underlying myometrium to labor-inducing hormones. Here, we demonstrate that within minutes, progesterone inhibits oxytocin- and bradykinin-induced contractions of rat uteri, calcium responses induced by platelet-activating factor in the human endometrial cell line MFE-280, and oxytocin-induced calcium signals in PHM1-31 immortalized pregnant human myometrial cells. Using human embryonic kidney (HEK293) cells as model system, we analyzed the molecular mechanisms underlying these effects. Our data indicate that progesterone rapidly depletes intracellular calcium stores. The resulting desensitization of the cells might contribute to the quiescence of the uterus during pregnancy.
Gehrig-Burger
Katja
K
Institute of Pharmaceutics and Biochemistry, University of Mainz, 55099 Mainz, Germany. kburger@uni-mainz.de
Slaninova
Jirina
J
Gimpl
Gerald
G
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004717:Endometrium / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology; D004971:Estrus; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000502:physiology
D043562:Receptors, G-Protein-Coupled; D000431:Ethanol; D011374:Progesterone; D004958:Estradiol; D010121:Oxytocin; D009543:Nifedipine; D002118:Calcium