PT - JOURNAL ARTICLE AU - Dongfang Liu AU - Kenneth A. Bachmann TI - An Investigation of the Relationship Between Estrogen, Estrogen Metabolites and Blood Cholesterol Levels in Ovariectomized Rats DP - 1998 Jul 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 561--568 VI - 286 IP - 1 4099 - http://jpet.aspetjournals.org/content/286/1/561.short 4100 - http://jpet.aspetjournals.org/content/286/1/561.full SO - J Pharmacol Exp Ther1998 Jul 01; 286 AB - 17β-Estradiol (E2) has long been known for protecting against coronary heart disease by lowering cholesterol levels in premenopausal women. A recent study in our laboratory suggested that two hydroxylated metabolites of E2 possess similar hypocholesterolemic effects in male rats. This effect has been further investigated with additional estrogen metabolites in ovariectomized rats with a view toward mimicking the true postmenopausal situation in humans. Their effects in reproductive tissues were also evaluated histologically. Fundamentally, the following issues were addressed: (1) Do oxidized metabolites of estradiol lower total cholesterol levels? (2) Can a hypocholesterolemic effect be achieved without eliciting estrogenic activities on reproductive tissues? The results of this investigation showed that a number of oxygenated metabolites of estradiol can lower cholesterol levels. Among them, 4-hydroxyestradiol (4-OHE2) produced a striking hypocholesterolemic effect and a substantial uterotropic effect. 2-Hydroxyestradiol (2-OHE2), 2-methoxyestradiol (2-meoE2) and 2-methoxyestrone (2-meoE1) produced a significant decrease in cholesterol levels at doses that did not produce significant uterotropic effects. The American Society for Pharmacology and Experimental Therapeutics