Insulin is the essential factor maintaining the constitutive expression ofhepatic sterol 14-demethylase P450 (CYP51)

The role of serum insulin in regulating the expression level of hepatic ste rol 14-demethylase P450 (CYP51) was examined. Administration of streptozoto cin, which destroys pancreatic beta-cells, caused reduction of CYP51 mRNA l evel in rats in parallel with the loss of serum insulin. Streptozotocin tre atment also reduced the CYP51 activity. The decreased mRNA level and activi ty of the streptozotocin-treated rats were restored to the normal level wit hin 24 h by repeated administration of insulin. CYP51 level of normal rats was insensitive to the circadian variation of serum insulin and insulin adm inistration, and no significant difference was observed between the hepatic CYP51 activities of Sprague-Dawley and Wistar lean rats, although the seru m insulin concentration of the latter was higher than the former. These fac ts indicate that the expression of hepatic CYP51 is maintained by serum ins ulin, and its lowest physiological level is sufficient for supporting the e xpression of CYP51, The responses of CYP51 expression to streptozotocin and insulin treatments were closely similar to those of the sterol regulatory element binding protein (SREBP)-1c expression [Shimomura ct al. (1999) Proc . Not. Acad. Sci, USA 96, 13656-13661]. Based on this fact, the possible co ntribution of SREBP-1c to the insulin-dependent expression of hepatic CYP51 gene was also discussed.