The suppressive effect of the catatoxic steroid, pregnenolone-16alpha-carbonitrile, on liver microsomal cholesterol-7alpha-hydroxlyase.

The effect of the catatoxic steroid, 3beta-hydroxy-20-oxo-5-pregnene-16alpha-carbonitrile [pregnenolone-16alpha-carbonitrile (PCN)] on hepatic microsomal cholesterol-7alpha-hydroxylase, the probable rate-limiting enzyme of bile acide biosynthesis, has been studied. Short term administration (3 days) of PCN in the diet of rats resulted in a significant decrease in the liver microsomal cholesterol-7alpha-hydroxylase activity, in contrast to a marked stimulation of microsomal cytochrome P-450 and ethylmorphine demethylase activity. PCN significantly depressed the cholesterol-7alpha-hydroxylase activity in the livers of rats with elevated levels of the enzyme produced by cholestyramine feeding. The results indicate the presence of separate control mechanisms in the regualtion of bile acid synthesis and drug metabolism.