Analysis of sex hormone-responsive element in sexually dimorphicly expressing CYP2B subfamily gene

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CYP2B subfamily constitutively and sexually dimorphicly expresses in the liver. In the mouse, the expression in female is far higher than that in male and the expressed species are different between male (Crp2b10>Cyp2b9) and female (Cyp2b9>Cyp2b10). The expression of these species is inducible by phenobarbital (PB), and the induction mechanism has been extensively revealed at molecular level. However, the mechanism of their constitutive expression has been scarcely investigated.Female and glucocorticoid hormones may participate the expression of Cyp2b9 and Cyp2b10, respecitively, and the latter hormone simultaneously suppresses Cyp2b9 expression. The role of male hormone is also considered to suppress Cyp2b9 expression. The sequence from -2331 to -2281 bp of the 5'-flanking region of Cyp2b10 gene is revealed to be responsible for the estradiol induction using luciferase assay. This region corresponds to the core element of PB-responsive enhancer module (PBREM). Several nucleotide mutations in the PBREM core element show that the NR1 (nuclear receptor 1) site is required for estradiol induction, the same element required for PB induction. The element also plays a critical role for induction by DDT, indicating that NR1 site responds to structurally-diversed inducers. Although Cyp2b9 is a major species expressed in female liver, no information is available for its expression mechanism, but estradiol is found as a potent inducer for investigating of the regulatory pathway.