Modulation of rat hepatic microsomal testosterone hydroxylases by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related toxic isostereomers.
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The effects of several toxic halogenated aryl hydrocarbons including 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran, 2,3,4,7,8-pentachlorodibenzofuran, 3,3',4,4'-tetrabromobiphenyl, 3,3',4,4'5-pentachlorobiphenyl, and 3,3',4,4'-tetrachloroazobenzene on hepatic microsomal testosterone hydroxylases were determined in the immature male rat. All of these compounds induced hepatic testosterone 7 alpha-hydroxylase and inhibited testosterone 6 beta-, 16 alpha-, 16 beta-, and 2 alpha-hydroxylases and androstenedione formation. It was observed that there was a good correlation between the increase in testosterone 7 alpha-hydroxylase by the halogenated hydrocarbons and their ability to cause body weight loss in the exposed rats. Comparable linear correlations were observed between toxicity and the decreased activities of other testosterone hydroxylases. The role of altered testosterone metabolism in the toxicity of halogenated aryl hydrocarbons is unknown.