Institute of Pharmaceutics and Biochemistry, University of Mainz, 55099 Mainz, Germany.
Cell Mol Life Sci. 2010 Aug;67(16):2815-24. doi: 10.1007/s00018-010-0360-4. Epub 2010 Apr 8.
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.
孕激素非基因组地减弱了人催产素受体和其他几种 Gq 蛋白偶联受体的钙信号。在妊娠期间,子宫内膜中孕激素浓度升高,拮抗了子宫平滑肌对分娩诱导激素的反应性。在这里,我们证明孕激素在几分钟内即可抑制大鼠子宫的催产素和缓激肽诱导的收缩、人子宫内膜细胞系 MFE-280 中血小板激活因子诱导的钙反应,以及 PHM1-31 永生化妊娠人子宫平滑肌细胞中的催产素诱导的钙信号。我们使用人胚肾 (HEK293) 细胞作为模型系统,分析了这些效应的分子机制。我们的数据表明,孕激素迅速耗竭细胞内钙储存。由此产生的细胞脱敏可能有助于妊娠期间子宫的静止。