Down-regulation of Gucocorticoid Receptor mRNA by Glucocorti-coids in Rats / 第二军医大学学报

ABSTRACT

The effect of glucocorticoids on the down-regulation of glucocorticoid receptor (GR) mRNA was studied in intact rats. GR mRNA was characterized by Northern blot hybridization and quantitated by dot blot hybridization using a human GR cDNA fragment as a probe. Administration of hydrocortisone in polyvinyl alcohol resulted in a rapid increase in plasma glucocorticoids which maintained at stress levels (20 to 40 ?g/dl) for about 3 d. Hepatic GR mRNA decreased significantly to 73.5?63% of control values 6 h following hydrocortisone treatment, after which the decline of GR mRNA was gradual, reaching a minimum of 44.0?5.0% of control levels 3 d after the treatment The effect of hydrocortisone on the down-regulation of hepatic GR mRNA lasted up to 11 d. In contrast, hydrocortisone treatment had no effect on GR mRNA in rat brain. These results are consistent with the changes in GR in rats as reported previously, except that even though the hepatic cytosol GR decreased markedly, no significant changes in hepatic GR mRNA were found 1 h after hydrocortisone treatment, strongly suggesting that the down-regulation of GR by its ligands in vivo occurs at both transcriptional and posttranscriptional levels and is of tissue-specific fashion.