Collaborating interaction of hormones for sex-dependent expression of CYP2B family

CYP2B9是小鼠肝脏中P450的组成型和雌性特异性表达亚型。垂体切除术诱导男性CYP2B9 mRNA表达水平与女性相似，而手术对女性无影响。模拟雄性生长激素分泌模式的生长激素（GH）每日注射两次，可显著抑制垂体切除术诱导的雄性mRNA表达。同样的处理完全抑制了完整雌性的表达。合成糖皮质激素地塞米松（DEX）抑制了完整雌性小鼠CYP2B9 mRNA的表达，但在gh处理和未处理的垂体切除雌性小鼠中没有。在原代培养的小鼠肝细胞中，天然糖皮质激素（如氢化可的松、皮质酮）和DEX可浓度依赖性地抑制CYP2B9 mRNA的表达。强效抗糖皮质激素RU486可部分抑制糖皮质激素介导的抑制作用。相反，RU486本身抑制CYP2B9 mRNA的表达。这些观察结果表明，CYP2B9的两性二态表达部分是由于男性血浆GH谱和糖皮质激素的抑制。

CYP2B9 is a constitutively and female-specifically expressed P450 isoform in mouse livers. Hypophysectomy-induced CYP2B9 mRNA expression in males to a level similar to that in females, while the operation did not affect females. Twice-daily injection of growth hormone (GH), which mimics the male pattern of GH secretion, significantly repressed hypophysectomy-induced mRNA expression in males. The same treatment completely suppressed expression in intact females. Treatments with synthetic glucocorticoid dexamethasone (DEX) suppressed expression of CYP2B9 mRNA in intact females, but not in GH-treated and un-treated hypophysectomized females. In primary cultured mouse hepatocytes, CYP2B9 mRNA expression was concentration-dependently suppressed by natural glucocorticoids such as hydrocortisone and corticosterone as well as by DEX. Glucocorticoid-mediated suppression was partially inhibited by RU486, a potent antiglucocorticoid. In contrast, RU486 by itself suppressed expression of CYP2B9 mRNA. These observations suggest that the sexually dimorphic expression of CYP2B9 is partly due to suppression by the masculine plasma GH profile and by glucocorticoid hormones.