Hayashi Y, Yamaguchi S, Pohlenz J, Murata Y, Refetoff S, Seo H
Department of Endocrinology and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Japan.
Mol Cell Endocrinol. 1997 Jul 4;131(1):59-66. doi: 10.1016/s0303-7207(97)00089-0.
Tissue responsiveness to a hormone is dependent on the amounts of its receptor expressed under physiological conditions. In the present report, we compared the magnitude of ligand-dependent transactivation mediated by two nuclear hormone receptors, thyroid hormone receptor beta (TR) and retinoid X receptor alpha (RXR), when overexpressed in a variety of cell lines. TR, RXR and reporter (luciferase) genes under the control of artificial hormone response elements were introduced into the cells using recombinant adenovirus (Ad) vectors, to ensure highly efficient gene delivery. Although the amounts of TR expressed were similar in the cell lines infected with Ad-TR, T3 dependent induction of reporter gene expression was significantly greater in HepG2 than in Cos7, GH3, or JEG3 cells, indicating that factors other than TR are limiting the responsiveness to T3. The enhanced response to 9-cis retinoic acid in cells overexpressing RXR was much greater in JEG3 than in HepG2 which had the highest responsiveness to T3 under TR overexpression. These results indicate that the factors affecting T3 responsiveness are not identical to those affecting the 9-cis retinoic acid responsiveness. On the other hand, overexpression of RXR in addition to TR resulted in a decrease in T3-responsiveness in all the cell lines tested, suggesting that some cofactors are common to TR and RXR.
组织对激素的反应性取决于其在生理条件下所表达的受体数量。在本报告中，我们比较了两种核激素受体，即甲状腺激素受体β（TR）和维甲酸X受体α（RXR）在多种细胞系中过表达时介导的配体依赖性反式激活的程度。利用重组腺病毒（Ad）载体将处于人工激素反应元件控制下的TR、RXR和报告基因（荧光素酶）导入细胞，以确保高效的基因传递。尽管在感染Ad-TR的细胞系中TR的表达量相似，但报告基因表达的T3依赖性诱导在HepG2细胞中比在Cos7、GH3或JEG3细胞中显著更强，这表明除TR外的其他因素限制了对T3的反应性。在过表达RXR的细胞中，对9-顺式视黄酸的增强反应在JEG3细胞中比在TR过表达时对T3反应性最高的HepG2细胞中要大得多。这些结果表明，影响T3反应性的因素与影响9-顺式视黄酸反应性的因素并不相同。另一方面，除TR外RXR的过表达导致在所有测试的细胞系中T3反应性降低，这表明某些辅因子是TR和RXR所共有的。
