STAT5b is required for GH-induced liver IGF-I gene expression.
STAT5b is required for GH-induced liver IGF-I gene expression.
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DOI：
10.1210/endo.142.9.8400
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发表时间：
2001-09
期刊：
影响因子：
4.8
通讯作者：
H. W. Davey;Tao Xie;Tao Xie;Michael J Mclachlan;R. Wilkins;D. Waxman;D. Grattan
中科院分区：
文献类型：
--
作者：
H. W. Davey;Tao Xie;Tao Xie;Michael J Mclachlan;R. Wilkins;D. Waxman;D. Grattan
虽然肝中Igf-I的表达增加响应GH的特点是，介导这种效果的细胞内信号通路尚未确定。属于Janus激酶-信号转导子和转录激活子5 b（JAK 2-STAT 5 b）途径的细胞内信号分子被GH激活，并且先前已被证明是两性异形体生长和肝脏细胞色素P450蛋白表达所需的，已知肝脏细胞色素P450蛋白表达受垂体GH分泌的性别特异性时间模式调节。在这里，我们评估的作用，STAT 5 b在GH激活的Igf-I通过监测诱导的Igf-I mRNA的野生型和Stat 5 b（-/-）小鼠的肝脏刺激外源性脉冲的GH。GH在切除垂体的雄性野生型小鼠中诱导肝脏Igf-I mRNA的表达，但在切除垂体的雄性Stat 5 b（-/-）小鼠中不诱导肝脏Igf-I mRNA的表达，尽管Stat 5 b（-/-）小鼠表现出正常的肝脏GH受体表达和细胞因子诱导的SH 2蛋白（Cis）的强烈GH诱导，这被认为有助于GH诱导的肝脏STAT 5 b信号转导的下调。因此，STAT 5 b在肝脏Igf-I基因表达中起着重要而特异的作用。
Although the increased expression of Igf-I in liver in response to GH is well characterized, the intracellular signaling pathways that mediate this effect have not been identified. Intracellular signaling molecules belonging to the Janus kinase-signal transducer and activator of transcription 5b (JAK2-STAT5b) pathway are activated by GH and have previously been shown to be required for sexually dimorphic body growth and the expression of liver cytochrome P450 proteins known to be regulated by the gender-specific temporal patterns of pituitary GH secretion. Here, we evaluate the role of STAT5b in GH activation of Igf-I by monitoring the induction of Igf-I mRNA in livers of wild-type and Stat5b(-/-)mice stimulated with exogenous pulses of GH. GH induced the expression of liver Igf-I mRNA in hypophysectomized male wild-type, but not in hypophysectomized male Stat5b(-/-) mice, although the Stat5b(-/-) mice exhibit both normal liver GH receptor expression and strong GH induction of Cytokine-inducible SH2 protein (Cis), which is believed to contribute to the down-regulation of GH-induced liver STAT5b signaling. Thus, STAT5b plays an important and specific role in liver Igf-I gene expression.