Alterations of plasma HDL lipids and apolipoproteins in female rats treated with ethynyl estradiol.

Female Sprague-Dawley rats (160-200 g body weight) were injected subcutaneously daily for 14 days with 1, 5, 15, 50 or 100 micrograms ethynyl estradiol in sesame oil/kg body weight, or with oil alone. Food consumption was restricted to 15 g/day, and animals were fasted overnight before exsanguination. Concentrations of plasma cholesteryl ester decreased with increasing dosage of ethynyl estradiol, as a result of decreases in HDL cholesteryl ester. Concentrations of plasma unesterified cholesterol were not altered by treatment; the tendency for a decrement in the HDL cholesterol was not statistically significant. Plasma and HDL phospholipid also tended to decrease with increasing dose of ethynyl estradiol. Plasma levels of apolipoprotein A-I increased on treatment with 5 micrograms ethynyl estradiol/kg but were diminished at a dose of 50 micrograms ethynyl estradiol/kg. The ultracentrifugally isolated high density lipoproteins were delipidated and the distribution of apolipoproteins was characterized by SDS-polyacrylamide gel electrophoresis and esoelectric focusing. The proportion of apolipoprotein E in HDL was depressed, while apolipoprotein A-I was increased and apolipoprotein C unchanged by treatment with ethynyl estradiol. Clearly, the alterations in plasma HDL lipid levels resulting from treatment with ethynyl estradiol were accompanied by distinct changes in composition of the apolipoproteins of HDL, and a biphasic response dependent on dose of the drug. A possible mechanism for the diminution in the proportion of HDL apolipoprotein E may be the enhanced removal of the apolipoprotein E-rich (HDL1) subfraction of the HDL from the circulation on treatment with ethynyl estradiol.