Mechanism of glucocorticoid receptor down-regulation by glucocorticoids.

作者：Stefan Rosewicz, Alex R. McDonald, Betty A. Maddux, Ira D. Goldfine, Roger L. Miesfeld, Craig D. Logsdon · 发表于：Journal of Biological Chemistry · 年份：1988 · DOI：10.1016/s0021-9258(18)69104-5 · 被引用次数：326 · 研究领域：Estrogen and related hormone effects、Adrenal Hormones and Disorders、Steroid Chemistry and Biochemistry

The effect of glucocorticoids on the regulation of glucocorticoid receptor mRNA was studied in two different cell lines, human IM-9 lymphocytes and rat pancreatic acinar AR42J cells. Using a glucocorticoid receptor cDNA probe, glucocorticoid receptor mRNA was examined by Northern blot hybridization and quantitated by slot-blot hybridization. In IM-9 and AR42J cells, dexamethasone decreased steady-state glucocorticoid receptor mRNA levels to approximately 50% of control. This decrease occurred with a one-half time of 3 h for IM-9 cells and 6 h for AR42J cells. Dexamethasone was the most potent steroid tested with a one-half maximal effect occurring at 10 nM and a maximal effect occurring at 100 nM. Glucocorticoid receptor mRNA half-life and gene transcription were then studied to determine the mechanism of decreased mRNA levels. The glucocorticoid mRNA half-life was approximately 120 min in IM-9 cells and 240 min in AR42J cells; these rates were not affected by dexamethasone treatment. In contrast, the rate of glucocorticoid gene transcription as measured by run-on assays in IM-9 cells was decreased to 50 +/- 6% of control by dexamethasone. These results indicate therefore that glucocorticoids regulate glucocorticoid receptor mRNA levels by influencing gene transcription.