Down-regulation of glucocorticoid receptor mRNA by glucocorticoids in rats

The effect of glucocorticoids on the down-regulation of glucocorticoidreceptor (GR) mRNA was studied in intact rats.GR mRNA was characterized byNorthern blot hybridization and quantitated by dot blot hybridization using a hu-man GR cDNA fragment as a probe.Administration of hydrocortisone (F) inpolyvinyl alcohol (PVA) resulted in a rapid increase in plasma glucocorticoidswhich maintained at stress levels (20 to 40μg/dl) for about 3 d.HepaticGR mRNA decreased significantly to 73.5±6.3% of control values 6h followingF treatment,after which the decline of GR mRNA was gradual,reaching a mini-mum of 44.0±5.0% of control levels 3d after the treatment.The effect of F onthe down-regulation of hepatic GR mRNA lasted up to 11 d.In contrast,F treat-ment had no effect on GR mRNA in rat brain.These results are consistent withthe changes in GR in rats as reported previously,except that even though thehepatic cytosol GR decreased markedly,no significant changes in hepatic GRmRNA were found 1h after F treatment,strongly suggesting that thedown-regulation of GR by its ligands in vivo occurs at both transcriptional andposttranscriptional levels and is of tissue-specific fashion.