Factors Influencing Regulation of CYP2B Expression

Abstract

ABSTRACTCytochrome P450 (P450) enzymes participate in a wide array of metabolic reactions. Of these P450s, CYP2B subfamily plays animportant role in the metabolism of endogenous compounds and xenobiotics. CYP2B1 and CYP2B2 in rats and CYP2B9 and CYP2B10in mice are major CYP2B isoenzymes constitutively and inducible expressed. Their constitutive expression is sexually dimorphic,specifically more expression in male than female rats, and more in female than male mice. Recent studies have shown that regulation ofCYP2B expression is markedly influenced by not only various endogenous and exogenous compounds, but also age, sex, strain, andnutritional status. Regarding regulation of P450 expression in mouse liver, a C57BL/6 strain is one of the most suitable mouse modelsbecause of its marked response to CYP2B induction. The regulation of sexual dimorphism of CYP2B highly depends on numerousendogenous hormones including glucocorticoids, sex hormones and growth hormones. Adrenalectomy suggested that glucocorticoidsinduced CYP2B10 but simultaneously suppressed CYP2B9 expression in both sexes. β-estradiol (ES) up-regulated the expression ofCYP2B9, while testosterone showed reverse activity of ES. Hypophysectomy and the age-expression profile revealed that growthhormone (GH) exerts suppressive effect on regulation of CYP2B9 and CYP2B10 expression in the males, but only on CYP2B10 in thefemales. Xenobiotics, i.e., phenobarbital, dexamethasone, DDT (1, 1, 1-trichloro-2, 2-bis (p-chlorophenyl) ethane), are exogenous factorsinfluencing the CYP2B expression. For example, phenobarbital and DDT induce both CYP2B9 and CYP2B10 while dexamethasonepredominantly induces CYP2B10, but simultaneously suppresses CYP2B9. Therefore, the factors that affect regulation of CYP2Bexpression should be thoroughly considered to eliminate their confounding effects, leading to accurate and precise outcome measures.Keywords: CYP2B, C57BL/6, sexual dimorphism, endogenous hormones, xenobioticsThai Pharm Health Sci J 2009;4(4):524-531§