Effects of clofibrate on the metabolism of progesterone and oestradiol in rat liver microsomal fraction

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Abstract
1. The substrate conversion of [4-14C]progesterone and [4-14C]oestradiol during incubation with the liver microsomal fraction from both control and clofibrate-treated rats amounted to about 10–15 and 20–25% respectively. 2. The metabolites of progesterone formed by preparations from control rats were hydroxylated in the 16α-position (14%), the 6β-position (12%) and the 2α-position (7%). Of the products formed from oestradiol 12% were recovered as a 16α-hydroxylated derivative whereas 5% had a 6β- and 2% a 6α-hydroxyl group. 3. Clofibrate affected the microsomal metabolism of both progesterone and oestradiol. It induced 7α-hydroxylation of both compounds, metabolic conversions not found in control rats. The 6β-hydroxylation of progesterone and the 6α-hydroxylation of oestradiol were enhanced by a factor of 2 and 3.5 respectively. The 2α-hydroxylation, and the 20α- and 20β-hydroxy steroid reduction of progesterone were significantly decreased as were the 16α- and the 6β-hydroxylation of oestradiol.