Thomas Peter, Pang Yefei
University of Texas at Austin, 750 Channel View Drive, Port Aransas, TX 78373, USA.
Steroids. 2013 Jun;78(6):583-8. doi: 10.1016/j.steroids.2013.01.003. Epub 2013 Jan 25.
The protective functions of progesterone in the cardiovascular system have received little attention even though evidence has accumulated that progesterone lowers blood pressure, inhibits coronary hyperactivity and has powerful vasodilatory and natriuretic effects. One possible reason why potential beneficial actions of progesterone on cardiovascular functions have not been extensively studied is that divergent effects to those of progesterone have been observed in many clinical trials with synthetic progestins such as medroxyprogesterone acetate which are associated with increased risk of coronary disease. Evidence that progesterone exerts protective effects on cardiovascular functions is briefly reviewed. The finding that progesterone administration decreases blood vessel vasoconstriction in several animal models within a few minutes suggests that rapid, nongenomic progesterone mechanisms are of physiological importance in regulating vascular tone. Rapid activation of second messenger pathways by progesterone has been observed in vascular endothelial and smooth muscle cells, resulting in alterations in endothelial nitric oxide synthase (eNOS) activity and calcium influx, respectively. Both nuclear progesterone receptors (PRs) and novel membrane progesterone receptors (mPRs) are candidates for the intermediaries in these rapid, cell-surface initiated progesterone actions in endothelial and smooth muscle vascular cells. PRs have been detected in both cell types. New data are presented showing mPRα, mPRβ and mPRγ are also present in human endothelial and smooth muscle vascular cells. Preliminary evidence suggests mPRs mediate rapid progestin signaling in these endothelial cells, resulting in down-regulation of cAMP production and increased nitric oxide synthesis. The role of mPRs in progesterone regulation of cardiovascular functions warrants further investigation.
孕酮在心血管系统中的保护作用很少受到关注，尽管已有证据表明，孕酮可降低血压、抑制冠状动脉活动亢进，并具有强大的血管舒张和利钠作用。孕酮对心血管功能的潜在有益作用尚未得到广泛研究，一个可能的原因是，在许多使用合成孕激素（如醋酸甲羟孕酮）的临床试验中观察到了与孕酮不同的作用，这些作用与冠心病风险增加有关。本文简要综述了孕酮对心血管功能发挥保护作用的证据。在几种动物模型中，给予孕酮后几分钟内血管收缩就会减弱，这一发现表明，快速的非基因组孕酮机制在调节血管张力方面具有重要的生理意义。在血管内皮细胞和平滑肌细胞中均观察到孕酮可快速激活第二信使途径，分别导致内皮型一氧化氮合酶（eNOS）活性改变和钙内流。核孕酮受体（PRs）和新型膜孕酮受体（mPRs）都是这些在内皮细胞和平滑肌血管细胞中由细胞表面引发的快速孕酮作用的中介候选者。在这两种细胞类型中均检测到了PRs。新数据表明，人血管内皮细胞和平滑肌细胞中也存在mPRα、mPRβ和mPRγ。初步证据表明，mPRs在内皮细胞中介导快速的孕激素信号传导，导致cAMP生成下调和一氧化氮合成增加。mPRs在孕酮调节心血管功能中的作用值得进一步研究。
