Down-regulation of glucocorticoid receptor mRNA by glucocorticoid hormones and recognition by the receptor of a specific binding sequence within a receptor cDNA clone.

作者：Sam Okret, Lorenz Poellinger, Yu Dong, Jan-Ακε Gustafsson · 发表于：Proceedings of the National Academy of Sciences · 年份：1986 · DOI：10.1073/pnas.83.16.5899 · 被引用次数：258 · 研究领域：Estrogen and related hormone effects、Steroid Chemistry and Biochemistry、Pharmacological Effects and Assays

A cDNA clone for the rat glucocorticoid receptor (GR) was used to study mechanisms of GR mRNA regulation. Treatment of rat hepatoma culture cells with 0.5 microM dexamethasone caused a small, initial increase in the GR mRNA level after 6 hr as well as a 50% to 95% reduction of the GR mRNA level after 24 hr of incubation when studied by RNA blot hybridization. After 72 hr, the initial GR mRNA level was restored. The down-regulation of GR mRNA levels appears to be independent of protein synthesis, since it also was observed in the presence of cycloheximide. However, cycloheximide caused a 4-fold increase in intracellular levels of GR mRNA. Using an immunoprecipitation assay, we could demonstrate that the GR specifically interacts with a GR cDNA clone, which represents a 2.6-kilobase fragment of the 3' nontranslated region of the GR mRNA. Nuclease protection experiments indicate the presence of several internal GR-binding regions in the above fragment.