TY - JOUR T1 - Developmental Action of Estrogen Receptor-α Feminizes the Growth Hormone-Stat5b Pathway and Expression of <em>Cyp2a4 </em>and<em>Cyp2d9</em> Genes in Mouse Liver JF - Molecular Pharmacology JO - Mol Pharmacol SP - 473 LP - 477 DO - 10.1124/mol.56.3.473 VL - 56 IS - 3 AU - Tatsuya Sueyoshi AU - Norihiko Yokomori AU - Kenneth S. Korach AU - Masahiko Negishi Y1 - 1999/09/01 UR - http://molpharm.aspetjournals.org/content/56/3/473.abstract N2 - We have studied the roles of estrogen receptor-α (ERα) and the Stat5b form of STAT (signal transducers and activators of transcription) in sex-specific expression ofCyp2a4 (steroid 15α-hydroxylase) andCyp2d9 (steroid 16α-hydroxylase) genes using ERα-deficient mice. ERα deficiency resulted in the repression of the female-specific Cyp2a4 and expression of the male-specific Cyp2d9 genes, respectively in females. In ERα-deficient males, the Cyp2d9 gene continued to be expressed. Nuclear localization of Stat5b occurs in both sexes of ERα-deficient mice, although it is normally observed in only wild-type males. Nuclear localization of Stat5b correlates with the repression of Cyp2a4 and expression ofCyp2d9, respectively. Because Stat5b was not detectable in liver nuclear extracts prepared from hypophysectomized ERα-deficient females, the regulation by ERα appeared to be mediated through a pituitary hormone (i.e., growth hormone). Thus, ERα appears to play a key role in the mechanism that inhibits nuclear localization of Stat5b in female mice, leading to feminization of a ERα-GH-Stat5b pathway and Cyp expression. Defaulting to this ERα-dependent mechanism results in localization of Stat5b to nuclei, which masculinizes the expression of Cyp genes in male mice. ER -