Effect of 23-methyl-21-norcholest-5-ene-3β,23,25-triol on hepatic cholesterol 7α-hydroxylase activity in the rat

Abstract The oxygenated sterol 23-methyl-21-norcholest-5-ene-3β,23,25-triol (SC-31082) has previously been reported to suppress 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and to inhibit cholesterol ester accumulation. In view of these demonstrated activities and because of a lack of data concerning the effects of oxygenated sterols on other catabolic pathways for cholesterol, SC-31082 was evaluated for its effects on the rate-limiting enzyme in bile acid production, 7α-hydroxylase. The administration of SC-31082 to male rats (100 mg/kg) for 7 days resulted in a 2-fold increase of the specific activity of 7α-hydroxylase over that of control rats maintained under identical lighting conditions and this elevated activity was higher than that found in control rats at the peak of their circadian rhythm. Despite the sterol-induced elevated 7α-hydroxylase activity, there was no apparent reduction in either serum or hepatic microsomal cholesterol levels.