Glucocorticoid regulation of insulin receptor gene transcription in IM-9 cultured lymphocytes.
Glucocorticoid regulation of insulin receptor gene transcription in IM-9 cultured lymphocytes.
复制标题
糖皮质激素对 IM-9 培养淋巴细胞中胰岛素受体基因转录的调节。
DOI：
10.1172/jci113347
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Goldfine,ID
中科院分区：
文献类型：
--
作者：
McDonald,AR;Goldfine,ID
我们已经报道糖皮质激素增加靶细胞中稳态胰岛素受体mRNA水平。在本研究中，使用IM-9培养的人淋巴细胞，我们调查的机制负责这种糖皮质激素介导的胰岛素受体mRNA水平的增加。IM-9细胞与100 nM地塞米松孵育4小时刺激了多聚体和核胰岛素受体RNA的平行增加，表明糖皮质激素没有改变胰岛素受体RNA的核转运。地塞米松没有改变胰岛素受体mRNA的半衰期（t1/2 = 140 +/- 20分钟），表明糖皮质激素不影响mRNA的稳定性。此外，地塞米松诱导的胰岛素受体mRNA水平的增加并没有阻止预处理细胞放线菌酮表明糖皮质激素的作用是独立的新的蛋白质合成。当标记的成绩单，从核径流孵育，然后杂交到人胰岛素受体cDNA，转录活性增加三至四倍，观察。这种转录效应发生在稳态胰岛素受体mRNA水平增加之前，并且在相同的地塞米松浓度范围内。因此，这些研究表明糖皮质激素对胰岛素受体基因转录的直接影响，并证明胰岛素受体基因受激素控制。图片
We have reported that glucocorticoids increase steady state insulin receptor mRNA levels in target cells. In the present study using IM-9 cultured human lymphocytes, we investigated the mechanism responsible for this glucocorticoid mediated increase in insulin receptor mRNA levels. Incubation of IM-9 cells with 100 nM dexamethasone for 4 h stimulated a parallel increase in both polysomal and nuclear insulin receptor RNAs indicating that glucocorticoids did not alter the nuclear transport of insulin receptor RNA. Dexamethasone did not alter insulin receptor mRNA half life (t 1/2 = 140 +/- 20 min), indicating that glucocorticoids did not influence mRNA stability. Furthermore, the dexamethasone-induced increase in insulin receptor mRNA levels was not blocked by pretreatment of cells with cycloheximide indicating that the glucocorticoid effect was independent of new protein synthesis. When the labeled transcripts from nuclear run-off incubations were then hybridized to immobilize human insulin receptor cDNA, a three- to fourfold increase in transcriptional activity was observed. This transcriptional effect occurred before the increase in steady state insulin receptor mRNA levels and over the same range of dexamethasone concentrations. These studies indicate therefore a direct effect of glucocorticoids on insulin receptor gene transcription, and demonstrate that the insulin receptor gene is under hormonal control.Images