Estrogen decreases prostaglandin H synthase products from endothelial cells.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Estradiol acts through a receptor-dependent process to decrease PGHS-dependent products, thus further elucidating this novel effect of estradiol on the vascular system.
Stewart
K G
KG
Department of Obstetrics/Gynecology, University of Alberta, Edmonton, Canada.
Zhang
Y
Y
Davidge
S T
ST
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis / Q000096:biosynthesis; D000818:Animals; D002417:Cattle; D002460:Cell Line; D003331:Coronary Vessels; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D008833:Microcirculation; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000032:analysis / Q000096:biosynthesis
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D009573:Nitrites; D013629:Tamoxifen; D009569:Nitric Oxide; D004958:Estradiol; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011451:Prostaglandin-Endoperoxide Synthases