Insulin is the essential factor maintaining the constitutive expression of hepatic sterol 14-demethylase P450 (CYP51).
The role of serum insulin in regulating the expression level of hepatic sterol 14-demethylase P450 (CYP51) was examined. Administration of streptozotocin, which destroys pancreatic beta-cells, caused reduction of CYP51 mRNA level in rats in parallel with the loss of serum insulin. Streptozotocin treatment also reduced the CYP51 activity. The decreased mRNA level and activity of the streptozotocin-treated rats were restored to the normal level within 24 h by repeated administration of insulin. CYP51 level of normal rats was insensitive to the circadian variation of serum insulin and insulin administration, and no significant difference was observed between the hepatic CYP51 activities of Sprague-Dawley and Wistar lean rats, although the serum insulin concentration of the latter was higher than the former. These facts indicate that the expression of hepatic CYP51 is maintained by serum insulin, and its lowest physiological level is sufficient for supporting the expression 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 et al. (1999) Proc. Nat. Acad. Sci. USA 96, 13656-13661]. Based on this fact, the possible contribution of SREBP-1c to the insulin-dependent expression of hepatic CYP51 gene was also discussed.
Yamashita
C
C
School of Pharmaceutical Sciences and Interdisciplinary Institute for Bioscience, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
Kudo
M
M
Ishida
H
H
Noshiro
M
M
Aoyama
Y
Y
Yoshida
Y
Y
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D007267:Injections; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010088:Oxidoreductases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D058886:Sterol 14-Demethylase; D013311:Streptozocin / Q000633:toxicity; D013737:Testis / Q000187:drug effects / Q000201:enzymology
D007328:Insulin; D013311:Streptozocin; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase