Estrogen up-regulates hepatic expression of suppressors of cytokine signaling-2 and -3 in vivo and in vitro
Estrogen up-regulates hepatic expression of suppressors of cytokine signaling-2 and -3 in vivo and in vitro
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DOI：
10.1210/en.2004-0061
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发表时间：
2004-12-01
期刊：
影响因子：
4.8
通讯作者：
Leung, KC
中科院分区：
文献类型：
--
作者：
Leong, GM;Moverare, S;Leung, KC
细胞因子信号转导抑制因子（SOCS）是细胞因子作用的重要负调节因子。我们最近报道，雌激素刺激SOCS-2的表达，抑制生长激素信号在肾细胞。雌激素对其他组织中SOCS表达的影响尚不清楚。本研究的目的是在体内和体外研究雌激素是否影响生长激素的主要靶器官肝脏中SOCS的表达。通过DNA微阵列分析研究雌激素对卵巢切除小鼠体内肝脏的影响，这些小鼠缺乏雌激素受体（ER）-α、ER β或两者都缺乏，以及它们的野生型同窝仔。在体外，用逆转录定量PCR检测雌激素对人肝癌细胞SOCS表达的影响。长期（3周）雌激素治疗诱导野生型和ER β基因敲除小鼠的SOCS-2和-3肝脏表达增加2至3倍，但在缺乏ER α或两种ER亚型的小鼠中则没有。短期处理（24小时）增加了SOCS-3的mRNA水平，但没有SOCS-2。在培养的肝癌细胞中，雌激素以时间和剂量依赖的方式使SOCS-2和-3 mRNA水平增加2倍（P
Suppressors of cytokine signaling (SOCS) are important negative regulators of cytokine action. We recently reported that estrogen stimulates SOCS-2 expression and inhibits GH signaling in kidney cells. The effects of estrogen on SOCS expression in other tissues are unclear. The aim of this study was to investigate in vivo and in vitro whether estrogen affected SOCS expression in the liver, a major target organ of GH. The in vivo hepatic effects of estrogen on ovariectomized mice lacking estrogen receptor (ER)-alpha, ERbeta, or both and their wildtype littermates were examined by DNA microarray analysis. In vitro, the effects of estrogen on SOCS expression in human hepatoma cells were examined by reverse transcription quantitative PCR. Long-term (3 wk) estrogen treatment induced a 2- to 3-fold increase in hepatic expression of SOCS-2 and -3 in wild-type and ERbeta knockout mice but not in those lacking ERalpha or both ER subtypes. Short-term treatment (at 24 h) increased the mRNA level of SOCS-3 but not SOCS-2. In cultured hepatoma cells, estrogen increased SOCS-2 and -3 mRNA levels by 2-fold in a time- and dose-dependent manner (P