Catechol estrogens as inhibitors of leukotriene synthesis.
Estrogens have a beneficial effect on atherosclerosis and osteoporosis after menopause, but their exact mechanism of action is still unknown. The aim of the present study was to investigate the effects of estradiol and its metabolites catechol estrogens on arachidonic acid metabolism in vitro. Estradiol had no effect on arachidonic acid metabolism up to 33 microM in A23187-stimulated human whole blood. All catechol estrogens (2-hydroxyestradiol, 2-hydroxyestrone, 4-hydroxyestradiol and 4-hydroxyestrone) had similar kinds of actions on arachidonic acid metabolism, being over ten times more potent inhibitors of leukotriene synthesis (IC50 values 0.044-0.16 microM) than thromboxane (IC50 values 0.99-2.1 microM) and prostaglandin E2 synthesis (IC50 values 0.84-5.5 microM). It is suggested that some of the protective actions of estrogens--e.g., on atherosclerosis and osteoporosis--may be related to the inhibition of leukotriene synthesis by catechol estrogens.
Alanko
J
J
School of Medicine, Department of Pharmacology, Clinical Pharmacology and Toxicology, University of Tampere, Finland. bljual@uta.fi
Sievi
E
E
Lähteenmäki
T
T
Mucha
I
I
Vapaatalo
H
H
Parantainen
J
J
D001094:Arachidonate 5-Lipoxygenase / Q000097:blood / Q000378:metabolism; D016718:Arachidonic Acid / Q000097:blood / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D002393:Estrogens, Catechol / Q000494:pharmacology*; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D017999:Leukotriene E4 / Q000096:biosynthesis / Q000097:blood; D015289:Leukotrienes / Q000096:biosynthesis* / Q000097:blood; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood / Q000378:metabolism; D013268:Stimulation, Chemical; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D002393:Estrogens, Catechol; D007476:Ionophores; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D000001:Calcimycin; D004958:Estradiol; D013929:Thromboxane B2; D017999:Leukotriene E4; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone