AN INVESTIGATION OF THE RELATIONSHIP BETWEEN ESTROGEN, ESTROGEN METABOLITES AND BLOOD CHOLESTEROL LEVELS IN OVARIECTOMIZED RATS

17 beta-Estradiol (E-2) has long been known for protecting against cor onary heart disease by lowering cholesterol levels in premenopausal wo men. A recent study in our laboratory suggested that two hydroxylated metabolites of E-2 possess similar hypocholesterolemic effects in male rats. This effect has been further investigated with additional estro gen metabolites in ovariectomized rats with a view toward mimicking th e true postmenopausal situation in humans. Their effects in reproducti ve tissues were also evaluated histologically. Fundamentally, the foll owing issues were addressed: (1) Do oxidized metabolites of estradiol lower total cholesterol levels? (2) Can a hypocholesterolemic effect b e achieved without eliciting estrogenic activities on reproductive tis sues? The results of this investigation showed that a number of oxygen ated 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-OHE 2), 2-methoxyestradiol (2-meoE(2)) and 2-methoxyestrone (2-meoE(1)) pr oduced a significant decrease in cholesterol levels at doses that did not produce significant uterotropic effects.