Estrogen Upregulates Production of Prostacyclin through COX-2

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 8 No. 1 • January 2005


Estrogen Upregulates Production of Prostacyclin through COX-2

A new paper1 reports that estrogens that activate the estrogen alpha receptor (ERalpha) cause the upregulation of COX-2 in female mice, with a resulting increased production of prostacyclin (PGI2). Prostacyclin is known to provide atheroprotection by inhibiting platelet activation and vascular contraction and proliferation, inhibiting leukocyte-endothelial cell interactions, and inhibiting cholesteryl ester hydrolase.1 Atherosclerotic plaques have a decreased capacity to manufacture prostacyclin. The authors propose that these mechanisms are responsible for the protection against atherogenesis in female mice. The protective effect of estrogen was eliminated in ovariectomized female mice lacking the prostacyclin receptor.

Ovariectomized animals are used as models of oxidative stress. Hence, menopause and the decline of circulating estrogens contribute to aging and to the loss of protection against atherosclerosis by increasing oxidative stress and by the loss of ERalpha activation that increases prostacyclin. The paper warns that selective COX-2 inhibitors may be particularly problematic for women. (This suggests that a reanalysis of the results of the trials of estrogen effects on cardiovascular disease in women might be a good idea, since the concurrent use of COX-2 inhibitors was not corrected for.) They are especially concerned about the use of these drugs in juvenile arthritis, a disease that predominantly affects females.

  1. Egan et al. COX-2-derived prostacyclin confers atheroprotection on female mice. Science 306:1954-7 (2004); see also comments on this paper in Couzin. Estrogen’s ties to COX-2 may explain heart disease gender gap. Science 306:1277 (2004).

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