Estrogen decreases prostaglandin H synthase products from endothelial cells

OBJECTIVE: Because we showed recently that estrogen replacement prevents pr ostaglandin H synthase (PGHS)-dependent vasoconstriction in rats, the aim o f this study was to determine how estradiol affects production of PGHS-depe ndent eicosanoids. METHODS: Cultured bovine coronary microvascular endothelial cells were expo sed 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 (TXA(2)), prostacyclin (PGI(2)), and nitric oxide (NO) were m easured as their stable metabolites, thromboxane B-2 (TXB2), 6-keto prostag landin F-1 alpha (6-keto PGF(1 alpha)), and nitrite (NO2), respectively. RESULTS: Estradiol had no effect on nitrite production. However, exposure t o 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 PGF(1 alpha) to 35 +/- 19% a nd 17 +/- 11% of control, respectively. Prostaglandin H synthase expression was no altered by estradiol. However, the estrogen receptor inhibitor, tam oxifen, reversed the inhibitory effect of estradiol. CONCLUSION: Estradiol acts through a receptor-dependent process to decrease PGHS-dependent products, thus further elucidating this novel effect of est radiol on the vascular system. (J Soc Gynecol Investig 1999;6:322-7) Copyri ght (C) 1999 by the Society for Gynecologic Investigation.