EFFECT OF CARBON TETRACHLORIDE AND OTHER INHIBITORS OF DRUG METABOLISM ON THE METABOLISM AND ACTION OF ESTRADIOL-17 AND ESTRONE IN THE RAT

¹ The Wellcome Research Laboratories, Burroughs Wellcome and Company (U.S.A.) Inc., Tuckahoe, New York

The administration of carbon tetrachloride to immature female rats 24 hours before sacrifice inhibited the activity of enzymes in liver microsomes that hydroxylate estradiol-17 and estrone. The oral administration of as little as 0.06 ml/kg of carbon tetrachloride inhibited by 70% the in vitro metabolism of estrone by rat liver microsomes. The inhibitory effect of carbon tetrachloride administration on estrogen metabolism in vitro was reflected in vivo by an altered total body metabolism of estradiol-17 and estrone, by a potentiation of the uterotropic action of these estrogens and by an increased concentration of these estrogens in the uterus. In contrast to the effect of carbon tetrachloride on estrogen action, pretreatment of rats with tetrachloroethylene did not influence the action of estrone. -Diethylaminoethyldiphenyl-propylacetate (SKF 525A) or desmethylimipramine are inhibitors of drug metabolism that also potentiate the uterotropic action of estrone and increase the concentration of estrogen in the uterus.

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