DIFFERENCES IN DOWN-REGULATION OF GLUCOCORTICOID RECEPTOR MESSENGER-RNA BY CORTISOL PREDNISOLONE AND DEXAMETHASONE IN HELA-CELLS

Glucocorticoids regulate the levels of their cognate receptors in a nu mber of target tissues and in many different cell lines. We have compa red the effect of three glucocorticoids, cortisol and its synthetic de rivatives, prednisolone and dexamethasone, on the levels of glucocorti coid receptor (GR) mRNA in HeLa cells. Clinically, the synthetic deriv atives are more active in hormonal action and have a longer half-life than cortisol. In the present study, the amounts of GR mRNA in HeLa ce lls were examined by Northern blot hybridization after treatment with cortisol, prednisolone or dexamethasone. These glucocorticoids decreas ed GR mRNA levels differently. After 24 h treatment with 1 x 10(-5) M cortisol, GR mRNA levels were only marginally suppressed (90% of the c ontrol), while prednisolone and dexamethasone suppressed GR mRNA level s to 67 and 57%, respectively. These differences may relate to the bio logical activities of these glucocorticoids. In time course studies, G R mRNA levels of the cells treated with cortisol and prednisolone decr eased to the minimum levels within 4 h and then recovered gradually, w hile those treated with dexamethasone reached the minimum level at 8 h and remained suppressed for more than 24 h. These differences may rel ate to the biological half-lives of these glucocorticoids.