Eisen L P, Elsasser M S, Harmon J M
Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
J Biol Chem. 1988 Aug 25;263(24):12044-8.
Regulation of glucocorticoid receptor (GR) protein and mRNA were examined in the human leukemic T-cell line CEM-C7. Unlike other cells in which GR regulation has been examined, the growth of these cells is inhibited by glucocorticoids, leading to cell death. Treatment of glucocorticoid-sensitive CEM-C7 cells with 1 microM dexamethasone for 18 h resulted in an increase in both cytoplasmic and nuclear GR protein, as determined by immunoblotting with anti-human GR antisera. Analysis of GR mRNA levels by Northern blotting revealed a corresponding increase in mRNA in steroid-treated cells. An increase in GR mRNA was detectable after as little as 3 h of treatment with dexamethasone, and GR mRNA concentration continued to increase for at least 18 h, well before the onset of growth arrest or cell death. GR mRNA concentration was not altered after dexamethasone treatment of the glucocorticoid-resistant mutant cell line ICR27TK.3, which lacks functional GR. Thus, the increase in GR seen in glucocorticoid-sensitive cells is a GR-mediated response. These results are in sharp contrast to the down-regulation of GR reported in other cells and tissues, and suggest that regulation of the GR by its cognate ligand may be tissue-specific.
在人白血病T细胞系CEM-C7中检测了糖皮质激素受体（GR）蛋白和mRNA的调节情况。与其他已检测GR调节的细胞不同，这些细胞的生长受到糖皮质激素的抑制，导致细胞死亡。用1 microM地塞米松处理糖皮质激素敏感的CEM-C7细胞18小时后，通过用抗人GR抗血清进行免疫印迹测定，发现细胞质和细胞核中的GR蛋白均增加。通过Northern印迹分析GR mRNA水平，发现类固醇处理的细胞中mRNA相应增加。用地塞米松处理仅3小时后即可检测到GR mRNA增加，并且GR mRNA浓度至少持续增加18小时，远在生长停滞或细胞死亡开始之前。用地塞米松处理缺乏功能性GR的糖皮质激素抗性突变细胞系ICR27TK.3后，GR mRNA浓度未改变。因此，在糖皮质激素敏感细胞中看到的GR增加是一种GR介导的反应。这些结果与其他细胞和组织中报道的GR下调形成鲜明对比，并表明其同源配体对GR的调节可能具有组织特异性。
