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 estra diol and its metabolites catechol estrogens on arachidonic acid metabo lism in vitro. Estradiol had no effect on arachidonic acid metabolism up to 33 mu M in A23187-stimulated human whole blood. All catechol est rogens (2-hydroxyestradiol, 2-hydroxyestrone, 4-hydroxyestradiol and 4 -hydroxyestrone) had similar kinds of actions on arachidonic acid meta bolism, being over ten times more potent inhibitors of leukotriene syn thesis (IC50 values 0.044-0.16 mu M) than thromboxane (IC50 values 0.9 9-2.1 mu M) and prostaglandin E-2 synthesis (IC50 values 0.84-5.5 mu M ). It is suggested that some of the protective actions of estrogens-e. g., on atherosclerosis and osteoporosis-may be related to the inhibiti on of leukotriene synthesis by catechol estrogens. (C) 1998 Elsevier S cience Inc.