Reduced glucocorticoid responsiveness and receptor concentration in splenic leukocytes of senescent rats

Glucocorticoids are 63% less effective in inhibiting [5-3-h] uridine uptake by splenic leukocytes of senescent rats (24-14 months) than by those of mature adult animals (12-14 months). Scatchard analyses reveal 57% fewer specific glucocorticoid binding sites in cytosols of the senescent group. Reduced binding of cortisol by cytosol macromolecules of intact viable leukocytes at 37 degrees C is also apparent in the older rats. Specific binding of glucocorticoids to cytoplasmic macromolecules appears to be closely linked, if not required, for inhibition of [5-3-hi1 uridine uptake. This is evidenced by the fact that both inhibition and specific binding are simultaneously blocked by progesterone administration. In addition, the amount of specific binding as well as the degree of inhibition of [5-3-h] uridine uptake is concentration dependent up to 2. 10-6 M cortisol. Thus, decreased glucocorticoid reponsiveness in the cells from senescent rats appears to be due primarily to decreased concentrations of specific glucocorticoid receptors.