The dependence of specific nuclear binding of glucocorticoids by rat thymus cells on cellular ATP levels.

The specific, saturable, nuclear binding of corticosteroids by rat thymus cells has been studied. Both the accumulation and the retention of corticosteroids by the nuclei of rat thymus cells at 37 degrees C were dependent upon the metabolic state of the cells. Treatment of cells with 2,4-dinitrophenol in the absence of glucose inhibited both accumulation and retention in the cell nucleus; these effects could be only partially prevented by the addition of glucose. The presence or absence of glucose also influenced the level of nuclear binding in the absence of 2,4-dinitrophenol, and in all cases the levels of nuclear binding of corticosteroids were correlated with cellular ATP levels. The effects of other reagents on levels of ATP and cyclic AMP also showed that significant changes in the level of nuclear-bound steroid were always accompanied by parallel variations in ATP levels, although there were no such correlations with levels of cyclic AMP. The partial restoration of nuclear binding by glucose in cells previously treated with 2,4-dinitrophenol was unaffected by cycloheximiede although protein synthesis was inhibited. Possible mechanisms by which the corticosteroid receptor is converted to a form capable of binding steroids by a reaction which requires energy but not de nova protein synthesis are discussed.