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Effect of Estrogens on Rat Serum Cholesterol Concentrations: Consideration of Dose, Type of Estrogen, and Treatment Duration^*

L. F. FERRERI and H. K. NAITO

Research Division, Cleveland Clinic Foundation Cleveland, Ohio 44106

Abstract

Daily sc injections of estradiol (17β-estradiol-3-benzoate) were given to five groups of adult female rats in doses of 0.25 µg, 2.5 µg, 25 µg, 250 µg, and 2 mg. The rats were bled at 0, 2, 5, and 8 weeks after the initiation of hormone treatment. In a second experiment, five groups of rats received daily sc injections of mestranol (ethynyl estradiol-3-methyl ether) in doses of 0.025,0.25, 2.5, 25, and 250 µg. These rats were bled after 2 weeks of treatment. In the first experiment, estradiol produced a biphasic effect: high doses (250 µg and 2 mg) lowered serum cholesterol concentrations, whereas lower doses (2.5 and 25 µg) increased serum cholesterol concentrations. Mestranol did not elicit this biphasic response, but was found to be 100 times more potent than estradiol with respect to its cholesterol-lowering ability. Both estradiol and mestranol stimulated hypertriglyceridemia at the same dose level: 2.5 µg. At 250 µg, mestranol caused a marked lowering of serum triglyceride concentrations, which was apparently associated with a toxic effect on the liver. Biphasic effects with respect to serum lipoprotein patterns were also observed in the estradiol-treated rats. Several of the estradiol dose levels which had altered serum lipids in the early weeks ceased to be effective after a longer period of treatment. The results demonstrated that the effect of estrogen treatment on serum lipids is highly dependent on the variables of dose, treatment duration, and type of estrogen. (Endocrinology 102: 1621, 1978)

Footnotes

^* This study was supported in part by Grants HL-6835 and HL-5126 (NIH) and Grant 3084R (AHA, Northeast Ohio Affiliate, Inc.). Preliminary findings from this study were presented at the 61st Annual Meeting of the Federation of American Societies for Experimental Biology, 1977.

Present address: Virginia Polytechnic Institute and State University, Department of Dairy Science, Blacksburg, Virginia 24061.

To whom requests for reprints should be addressed.

Received September 6, 1977.

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