The molecular mechanism of the action of the pharmacological doses of glucocorticoids. Studies on the low-affinity glucocorticoid receptor.

The low-affinity glucocorticoid binding sites (LAGS, kDa 1-10 mumol/L) with glucocorticoid specificity were demonstrated in hepatic cytosol of rats. The induction of tyrosine aminotransferase (TAT) activity in primary cultures of rat hepatocytes by high concentration (10 mumol/L) of hydrocortisone (F) could be completely inhibited by RU486, the competitive antagonist of glucocorticoid receptor, indicating that the induction of TAT by high concentrations of F is mediated by LAGS, therefore, LAGS may be referred to as low-affinity glucocorticoid receptor (GRL). In order to study the effect of GC on GRL, the concentration of glucocorticoids (GC) in plasma was maintained over 1 mumol/L for 3 d by subcutaneous injection of F in polyvinyl alcohol into rats. The binding capacity (Ro) of high-affinity glucocorticoid receptor (GRH) decreased significantly 1 h after injection and maintained at low level, whereas the Ro of GRL increased at 1, 24, and 48 h after injection. Thus, it may be concluded that GC can downregulate GRH but upregulate GRL. These results strongly suggest that the action of pharmacological doses of GC may be mediated by GRL.