McKearin D M, Shapiro D J
Department of Biochemistry, University of Illinois, Urbana 61801.
J Biol Chem. 1988 Mar 5;263(7):3261-5.
Administration of estradiol-17 beta to male Xenopus laevis induces the hepatic mRNA coding for the serum retinol binding protein (RBP) approximately 10-fold, both in vivo and in primary liver cultures. Estrogen induction of RBP mRNA is completely blocked by the anti-estrogen, hydroxytamoxifen. Testosterone administration reduces the elevated level of RBP mRNA observed in livers of female X. laevis to the constitutive level seen in livers of control male animals, and partially blocks the estrogen induction of RBP mRNA. Intracellular RBP mRNA levels therefore represent a balance between the opposing effects of estradiol-17 beta and testosterone. In marked contrast to the estrogen induction of vitellogenin mRNA, which requires the continuous presence of exogenous estrogen, induction of RBP mRNA persists for at least 4 months after a single injection of estrogen. Runoff transcription measurements demonstrate that persistent induction of RBP mRNA is due to an increased rate of RBP gene transcription. Administration of hydroxytamoxifen abolishes persistent induction of RBP mRNA, suggesting that residual hormone receptor complex plays a role in the persistent induction of RBP gene transcription. The persistent estrogen induction of RBP mRNA provides the first demonstration of long-term activation of the transcription of a hormone-responsive gene in response to a transient dose of a steroid hormone.
给雄性非洲爪蟾注射17β-雌二醇，无论在体内还是在原代肝脏培养物中，均可诱导血清视黄醇结合蛋白（RBP）的肝mRNA增加约10倍。雌激素对RBP mRNA的诱导作用可被抗雌激素药物他莫昔芬完全阻断。给雌性非洲爪蟾注射睾酮后，其肝脏中升高的RBP mRNA水平降至对照雄性动物肝脏中的基础水平，并部分阻断雌激素对RBP mRNA的诱导作用。因此，细胞内RBP mRNA水平代表了17β-雌二醇和睾酮的相反作用之间的平衡。与需要持续存在外源性雌激素才能诱导卵黄蛋白原mRNA的雌激素诱导作用形成鲜明对比的是，单次注射雌激素后，RBP mRNA的诱导作用持续至少4个月。转录延伸测量表明，RBP mRNA的持续诱导是由于RBP基因转录速率增加所致。他莫昔芬的给药消除了RBP mRNA的持续诱导，提示残留的激素受体复合物在RBP基因转录的持续诱导中起作用。RBP mRNA的雌激素持续诱导首次证明了激素反应基因转录在对类固醇激素的短暂剂量反应中的长期激活。
