Mechanism of actions of glucocorticoid and appropriate methods of glucocorticoid administration.

Blood, liver cytosol and nuclear levels of a synthetic glucocorticoid, betamethasone were measured by the specific radioimmunoassay after administration to rats. Betamethasone receptor in liver cytosol was also measured by the 3H-betamethasone binding assay.Betamethasone levels in blood and liver cytosol reached peak levels 1 hour after oral administration and then decreased gradually. Nuclear betamethasone reached peak levels slightly later, compared to blood and cytosol betamethasone peaks. Betamethasone receptor in liver cytosol decreased in reversed relation to the increase in the nuclear betamethasone level.Glucocorticoid receptor mRNA levels, in cultured HeLa cells were only marginally suppressed by cortiso1 10-5M, while prednisolone and dexamethasone suppressed glucocorticoid receptor mRNA levels to 67% and 57% of the initial levels, respectively.Dynamic changes in tissue levels of the orally administred glucocorticoids as well as the changes in glucocorticoid receptor and its mRNA expression may give insight into the understanding of the molecular mechanism of antiinflammatory glucocorticoid actions.