Properties and dynamics of glucocorticoid binding capacity in rat skin

[3H]Dexamethasone binding was detected in cytosol prepared from rat skin only in the presence of dithiothreitol (DTT). Simultaneous supplement of sodium molybdate (Mo) induced synergistic enhancement of the binding. In the presence of DTT and Mo the dissociation constant was approximately 1 nM, the number of maximum binding sites was approximately 100-200 fmol/mg protein, and only steroids that possessed glucocorticoid activity competed with [3H]dexamethasone binding. [3H]Dexamethasone-receptor complexes in dermal cytosol were able to bind to DNA-cellulose after brief heating, and receptors were eluted from DEAE-cellulose with 0.2 M KCl. These observations showed that [3H]dexamethasone binding sites observed in dermal cytosols have similar binding characteristics to glucocorticoid receptors in other glucocorticoid target tissues. Binding capacity in dermal cytosols was depleted after in vivo administration of all 4 glucocorticoids used in the present study. Both the extent and the duration of depletion were dose-dependent in all instances. Non-fluorinated glucocorticoids required higher doses to induce a profound depletion than did fluorinated ones and the duration of depletion induced by the former was shorter than by the latter. Since fluorinated glucocorticoids usually have higher anti-inflammatory potency than non-fluorinated ones, we concluded that the pattern of depletion and replenishment of the dermal cytosol binding capacity was correlated with glucocorticoid biopotency.