Influence of clofibrate on liver microsomal hydroxylation of cholesterol and androstenedione

The liver microsomal metabolism of 4-[4-¹⁴C]androstene-3,17-dione and [4-¹⁴C]cholesterol was studied in control and clofibrate-treated rats. In the control rat 25 per cent of androstenedione metabolites were hydroxylated at the 6β-position. Another 25 per cent were recovered as 16-oxygenated derivatives and minor amounts (5 per cent) were hydroxylated at the 6α- or a 7α-position. Clofibrate stimulated all the hydroxylation reactions of this compound. The 6β-hydroxylation was elevated by 100 per cent, the 7α-hydroxylation by 70 per cent, and the 6α- and 16α-hydroxylations by 50 per cent. Furthermore, following treatment with clofibrate, the ratio between 17β-hydroxy-4-androstene-3,16-dione and 16α-hydroxy-5-androstene-3, 17-dione increased from 0.15 to 0.68. The activity of the 17β-hydroxysteroid oxido-reductase increased by 100 per cent, whereas the 3β-hydroxysteroid oxidoreductase and 5α-reductase activities were only slightly affected. The 7α-hydroxylation of labelled cholesterol was uninfluenced by treatment with clofibrate. It is suggested that clofibrate stimulates the activity of the enzyme system involved in the hydroxylation of drugs in the liver.