Effects of Pesticides and Related Compounds on Steroid Metabolism and Function

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Abstract
The studies reviewed were selected to describe those investigations that could provide mechanistic-biochemical interpretations for the effects of pesticides on steroid-mediated biological functions. Two major observations have been emphasized. The first reflects the ability of chlorinated hydrocarbons to induce the activity of hepatic drug-metbolizing enzymes (monooxygenases), and the second reflects the estrogenic action of certain DDT derivatives. The recognition by Conney, Kuntzman, and their colleagues that steroids can serve as endogenous substrates for the hepatic monooxygenase led to the subsequent demonstration that chlorinated hydrocarbons enhance the hepatic hydroxylation of various steroids, accompanied by a decrease in their biological activity. This decrease in biological activity of steroids exhibits itself in a decrease in the uterotropic response to estrogens, in a decrease in androgen-mediated elevation of seminal-vesicle weight, and in a diminution in the glucocorticoid induction of hepatic tyrosine transaminase. The estrogenicity of certain DDT derivatives was found both in mammals and birds. Among the DDT derivatives examined, o,p' DDT was found to be the most active. The mechanism of estrogenicity of the DDT derivatives has not been clarified. Certain studies utilizing CCl4, inhibition of hepatic enzymes suggest that DDT derivatives may be acting via their respective metabolites. On the other hand, studies based on the ability of DDT derivatives to interfere with estradiol-binding to the uterine cytosolic estrogen receptor suggest that they may be acting via the parent compounds per se. The latter findings also suggest that DDT derivatives bind to the 8s cytosolic receptor, which in turn suggests that their action mimics that of “true” estrogens. In addition, recent findings also show that chlorinated hydrocarbons act as antiandrogens in the male by interfering with the binding of dihydrotestosterone at its receptor site. The observations that chlorinated hydrocarbons may have estrogenic and antiandrogenic actions could be the reason for the contradictory findings in early investigations concerning effects on fertility and accessory sex organ development.

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