Effects of clofibrate on the metabolism of progesterone and oestradiol in rat liver microsomal fraction.
1. The substrate conversion of [4-(14)C]progesterone and [4-(14)C]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 16alpha-position (14%), the 6beta-position (12%) and the 2alpha-position (7%). Of the products formed from oestradiol 12% were recovered as a 16alpha-hydroxylated derivative whereas 5% had a 6beta- and 2% a 6alpha-hydroxyl group. 3. Clofibrate affected the microsomal metabolism of both progesterone and oestradiol. It induced 7alpha-hydroxylation of both compounds, metabolic conversions not found in control rats. The 6beta-hydroxylation of progesterone and the 6alpha-hydroxylation of oestradiol were enhanced by a factor of 2 and 3.5 respectively. The 2alpha-hydroxylation, and the 20alpha- and 20beta-hydroxy steroid reduction of progesterone were significantly decreased as were the 16alpha- and the 6beta-hydroxylation of oestradiol.
D000818:Animals; D002250:Carbon Radioisotopes; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D002994:Clofibrate / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism*; D006900:Hydroxylation; D008099:Liver / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size; D011374:Progesterone / Q000378:metabolism*; D011506:Proteins / Q000032:analysis; D051381:Rats
D002250:Carbon Radioisotopes; D011506:Proteins; D011374:Progesterone; D004958:Estradiol; D002994:Clofibrate