Different regulation of the expression of mouse hepatic cytochrome P4502B enzymes by glucocorticoid and phenobarbital

The effect of the synthetic glucocorticoid, dexamethasone, and phenobarbital upon the expression of Cyp2b9 and Cyp2b10, major CYP2B subfamilies in the mouse, was differentiated in C57BL/6 mouse liver and hepatocytes in primary culture. Overall expression was higher in the untreated female liver than in the male liver. More Cyp2b9 than Cyp2b10 mRNA was present in the female liver, whereas the level of Cyp2b10 was higher in the male. Phenobarbital increased Cyp2b10 expression more than did Cyp2b9 in both sexes, Treatment with dexamethasone markedly induced Cyp2b10 expression dose dependently, but simultaneously suppressed Cyp2b9 in both sexes. Evidence of this was obtained both in vivo and in hepatocyte culture. Furthermore, the existence of at least two unknown species of CYP2B, whose expressions were either increased or decreased by dexamethasone was suggested. Adrenalectomy increased the expression of Cyp2b9 and Cyp2b10 mRNAs, especially that of Cyp2b9 in the male liver. In addition, the expression of one unknown species which was constitutively suppressed increased in adrenalectomized male mice. That the treatment of dexamethasone or adrenalectomy altered the expression of CYP2B subfamilies suggests that endogenous glucocorticoid hormone plays a basic role in the constitutive expression of cytochrome P450, Furthermore, the sex-related difference in the expression of Cyp2b9 and Cyp2b10 suggests that sex-dependent secretion of endogeneous modulating factors is involved in the regulatory pathway. (C) 1999 Academic Press.