Estrogen decreases prostaglandin H synthase products from endothelial cells.

Abstract

Because we showed recently that estrogen replacement prevents prostaglandin H synthase (PGHS)-dependent vasoconstriction in rats, the aim of this study was to determine how estradiol affects production of PGHS-dependent eicosanoids. Cultured bovine coronary microvascular endothelial cells were exposed to physiologic levels of 17 beta-estradiol (0.01 nM [about 2.7 pg/mL], 0.1 nM [about 27 pg/mL], or 1.0 nM [about 270 pg/mL]) for 4, 8, or 24 hours. Thromboxane (TXA2), prostacyclin (PGI2), and nitric oxide (NO) were measured as their stable metabolites, thromboxane B2 (TXB2), 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), and nitrite (NO2), respectively. Estradiol had no effect on nitrite production. However, exposure to 0.1 nM and 1.0 nM estradiol for 24 hours reduced TXB2 production to 67 +/- 16% and 69 +/- 12% of control, respectively. Furthermore, 0.1 nM and 1.0 nM estradiol also reduced production of 6-keto PGF1 alpha to 35 +/- 19% and 17 +/- 11% of control, respectively. Prostaglandin H synthase expression was not altered by estradiol. However, the estrogen receptor inhibitor, tamoxifen, reversed the inhibitory effect of estradiol. Estradiol acts through a receptor-dependent process to decrease PGHS-dependent products, thus further elucidating this novel effect of estradiol on the vascular system.