Sick euthyroid syndrome is associated with decreased TR expression and DNA binding in mouse liver
Sick euthyroid syndrome is associated with decreased TR expression and DNA binding in mouse liver
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DOI：
10.1152/ajpendo.00155.2002
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发表时间：
2003-01-01
影响因子：
5.1
通讯作者：
Feingold, KR
中科院分区：
文献类型：
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作者：
Beigneux, AP;Moser, AH;Feingold, KR
感染与低血清甲状腺激素和促甲状腺激素水平有关。在这里，我们证明，感染也减少甲状腺激素受体（TR）的表达。在凝胶位移实验中，给予脂多糖（LPS）后4小时和16小时，小鼠肝脏中维甲酸X受体（RXR）/TR DNA结合分别减少60%和77%。令人惊讶的是，LPS在4 h时没有降低TR-α或TR-β蛋白水平，但到16 h时，TR-α（1）、TR-α（2）和TR-β水平分别降低了55%、87%和41%。我们以前报道过LPS迅速降低肝脏中RXR蛋白水平。因此，我们将RXR-β添加到LPS处理后4小时制备的肝核提取物中，其将RXR/TR DNA结合恢复到与对照相当的水平。对LPS给药后16小时制备的提取物进行的类似实验没有恢复RXR/TR DNA结合。我们认为RXR表达的降低限制了4 h时RXR/TR DNA结合，而TR和RXR水平的降低导致16 h时结合进一步降低。
Infection is associated with low serum thyroid hormones and thyrotropin levels. Here we demonstrate that infection also reduces thyroid hormone receptor (TR) expression. In gel shift experiments, retinoid X receptor (RXR)/TR DNA binding was reduced in mouse liver by 60 and 77%, respectively, 4 and 16 h after lipopolysaccharide (LPS) administration. Surprisingly, LPS did not decrease either TR-alpha or TR-beta protein levels at 4 h, but by 16 h TR-alpha(1), TR-alpha(2), and TR-beta levels were reduced by 55, 87, and 41%, respectively. We previously reported that LPS rapidly decreases RXR protein levels in liver. Therefore, we added RXR-beta to hepatic nuclear extracts prepared 4 h after LPS treatment, which restored RXR/TR DNA binding to a level comparable to that of controls. A similar experiment conducted on extracts prepared 16 h after LPS administration did not restore RXR/TR DNA binding. We propose that decreased RXR expression is limiting for RXR/TR DNA binding at 4 h, whereas the reduction in both TR and RXR levels results in further decreased binding at 16 h.