Protective actions of progesterone in the cardiovascular system: Potential role of membrane progesterone receptors (mPRs) in mediating rapid effects

被引:68
|
作者
Thomas, Peter [1 ]
Pang, Yefei [1 ]
机构
[1] Univ Texas Austin, Port Aransas, TX 78373 USA
关键词
Cardiovascular; Progesterone; Protective; Membrane progesterone receptors; Nuclear progesterone receptors; Nongenomic; NITRIC-OXIDE SYNTHASE; ESTROGEN PLUS PROGESTIN; HUMAN ENDOTHELIAL-CELLS; HYPERTENSIVE POSTMENOPAUSAL WOMEN; HORMONE REPLACEMENT THERAPY; INDUCED MYOCARDIAL-ISCHEMIA; AMBULATORY BLOOD-PRESSURE; CORONARY-ARTERY-DISEASE; SMOOTH-MUSCLE-CELLS; BREAST-CANCER CELLS;
D O I
10.1016/j.steroids.2013.01.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mPR alpha, mPR beta and mPR gamma 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. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:583 / 588
页数:6
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