CHARACTERIZATION OF THE OVARIECTOMIZED RAT MODEL FOR THE EVALUATION OF ESTROGEN EFFECTS ON PLASMA-CHOLESTEROL LEVELS

Estrogens protect against cardiovascular disease in women through effe cts on the vascular wall and liver. Here we further characterize tile rat as a model for the evaluation of estrogenic effects on plasma lipi d levels us. uterine wet weight. In adult ovariectomized female rats t reated for 4 days sc, 17 alpha-ethinyl estradiol (EE) was the most pot ent agent to lower plasma total and high density lipoprotein cholester ol levels, followed by 17 beta-estradiol and 17 alpha-estradiol. Howev er, 17 alpha-estradiol had the greatest separation of uterotropic us. cholesterol-lowering effects. EE had the same lipid-lowering potency w hether administered sc ol orally to adult rats. It had no effect on ch olesterol levels in immature rats, even though the uterotropic respons e was dramatic. Testosterone propionate, dexamethasone, and progestero ne did not significantly lower cholesterol levels. The antiestrogens t amoxifen and raloxifene lowered cholesterol levels, but with less effi cacy and potency than the estrogens. ICI 182780 had no effect on chole sterol levels. When coadministered with EE, ICI 182780 inhibited the c holesterol-lowering and uterotropic activities of EE, suggesting that the estrogen receptor pathway is involved. In conclusion, although the information from the rat is limited as a model of the low density lip oprotein-lowering effects of estrogens in humans, it can be used to st udy the effects and mechanism of action of estrogen and antiestrogens on plasma cholesterol levels.