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

The substrate conversion of [4 ¹⁴C]progesterone and [4 ¹⁴C]estradiol during incubation with the liver microsomal fraction from both control and clofibrate treated rats amounted to about 10 to 15 and 20 to 25% respectively. 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 estradiol 12% were recovered as a 16α hydroxylated derivative whereas 5% had a 6β and 2% a 6α hydroxyl group. Clofibrate affected the microsomal metabolism of both progesterone and estradiol. It induced 7α hydroxylation of both compounds, metabolic conversions not found in control rats. The 6β hydroxylation of progesterone and the 6α hydroxylation of estradiol 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 estradiol.