Biopotency and Nuclear Binding in Glucocorticoids

Nuclear binding abilities of 3 glucocorticoids, dexamethasone (Dex), prednisolone (Pred) and corticosterone (Cort), which exhibited different biopotencies were comparedin vitro. Cytosols labelled with 3H-Dex, 3H-Pred and 3H-Cort from the rat liver prepared by incubation at 0°C for 16hr were bound to isolated liver nuclei in rates of approximately 25%, 9% and 1% of added radioactivity, respectively. Nuclear binding rates observed were correlated with biopotencies of these steroids. Time course studies of the cytosol binding revealed that the difference in the nuclear binding ability of these ligands was attributable, at least in part, to the metabolic transformation of ligands during the incubation period. A significant portion of 3H-Pred and 3H-Cort was transformed to polar metabolite (s) even under the incubation conditions at 0°C. Kd's of the cytosol binding to 3H-Dex which was metabolically stable were decreased with the length of incubation time, significantly lower Kd being observed in the cytosol incubated for 16hr than in those incubated for 2 and 6hr. Kd's and the number of maximum binding sites were erratic when the ligands received biotransformation during the course of incubation. Transformed 3H-Pred and 3H-Cort during the incubation still exhibited features of the protein bound state. Besides biotransformation of ligands, structure related difference in the nuclear binding ability of these glucocorticoids was also observed. These observations suggest that metabolic susceptibility as well as structure related ability of the nuclear binding may contribute to the biopotency of glucocorticoids.