Kaiser A, Stier U, Riecken E O, Rosewicz S
Abteilung für Gastroenterologie, Klinikum Benjamin-Franklin, Freie Universität Berlin, Deutschland.
Digestion. 1996;57(3):149-60. doi: 10.1159/000201329.
In this study we investigated the effects of altered intracellular glucocorticoid receptor (GR) concentrations on glucocorticoid-regulated gene expression in the rat pancreatic acinar cell line AR42J. Incubation of AR42J cells with dexamethasone results in a time-dependent transcriptional stimulation of amylase gene expression (about 5-fold) and a transcriptional inhibition of bombesin receptor (BR) gene expression. Decreasing the intracellular GR concentration to 50% by preincubation with RU 38486 results in a significant attenuation of dexamethasone-regulated amylase and BR gene expression. In contrast, increasing the intracellular GR concentration 2-fold by preincubation with the phosphodiesterase inhibitor IBMX significantly enhances the glucocorticoid inhibition of BR gene expression whereas amylase mRNA concentrations remain unaltered. These data demonstrate that intracellular GR concentrations determine the sensitivity of glucocorticoid-regulated gene expression in rat pancreatic AR42J cells.
在本研究中，我们调查了细胞内糖皮质激素受体（GR）浓度改变对大鼠胰腺腺泡细胞系AR42J中糖皮质激素调节的基因表达的影响。用 dexamethasone 孵育 AR42J 细胞会导致淀粉酶基因表达的时间依赖性转录刺激（约 5 倍）以及蛙皮素受体（BR）基因表达的转录抑制。通过与 RU 38486 预孵育将细胞内 GR 浓度降低至 50%会导致 dexamethasone 调节的淀粉酶和 BR 基因表达显著减弱。相反，通过与磷酸二酯酶抑制剂 IBMX 预孵育使细胞内 GR 浓度增加 2 倍，会显著增强糖皮质激素对 BR 基因表达的抑制作用，而淀粉酶 mRNA 浓度保持不变。这些数据表明，细胞内 GR 浓度决定了大鼠胰腺 AR42J 细胞中糖皮质激素调节的基因表达的敏感性。
