INSECTICIDE INHIBITION AND STIMULATION OF STEROID HYDROXYLASES IN RAT LIVER

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

The in vitro addition of organic phosphorothionate insecticides, such as parathion, malathion and chlorthion, or halogenated hydrocarbon insecticides, such as chlordane and DDT, inhibited the liver microsomal hydroxylation of testosterone. Treatment of rats with chlorthion for 10 days inhibited the liver microsomal hydroxylation of testosterone, estradiol-17, progesterone and deoxycorticosterone, whereas chronic treatment of rats with chlordane or DDT stimulated the hydroxylation of these steroids. More detailed studies on the hydroxylation of testosterone in specific positions revealed that chlorthion had a more marked inhibitory effect on the 16-hydroxylation than on the 6-or 7-hydroxylation reaction. Chronic treatment of rats with chlordane or DDT stimulated the 6-, 7-and 16-hydroxylation of testosterone, but had a more marked stimulatory effect on the 16- hydroxylation reaction. These results suggest that the liver microsomal enzyme system responsible for the 16-hydroxylation of testosterone differs from the systems that 6-and 7-hydroxylate this steroid.

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