Anti-Hypercholesterolemic Effect of Dehydroepiandrosterone in Rats

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Abstract
Dehydroepi-androsterone (DHA) and 3[alpha]-methoxy-17[alpha]-methyl-5[alpha]-androstane-17a-01 (SC-12790) were studied for their anti-hypercholesterolemic and thyromimetic activities. The following findings were established DHA (5 mg/kg/orally, daily for 10 days) was an anti-hypercholesterolemic agent which prevented increase in serum cholesterol level (SLC) of rats made hypercholesterolemic by propylthiouracil (PTU) treatment. The same dose DHA given over a period of 21 days prevented an increase in SCL in rats made hypercholesterolemic by combined PTU and cholesterol. DHA, did not reduce the SCL or normal rats. SC-12790, when given under the same experimental conditions as DHA, did not reduce the SCL of hypercholesterolemic rats. DHA did not produce any change in thyroid weight as did exogenous TSH and T-3. The anti-hypercholesterolemic effect of DHA cannot be explained by a thyromimetic effect. These findings are of clinical importance since DHA, which is a weak endogenous androgen, is orally active as an anti-hypercholesterolemic agent. The possible mechanism of its action is discussed.