Age related changes in glucocorticoid binding by rat splenic leukocytes: Possible cause of altered adaptive responsiveness

Abstract

Splenic leukocytes of senescent rats (24 to 26 mth) exhibit a 60% reduction in cortisol induced inhibition of 3H uridine uptake when compared to mature adult animals (12 to 14 mth). The degree of inhibition is directly proportional to cortisol dosage up to 2 x 10-6M. Specific binding of physiological (nanomolar) concentrations of 3H cortisol by leukocytic cytosol macromolecules is reduced by over 40% in the older animals. Moreover, Scatchard analyses reveal 60% fewer specific glucocorticoid binding sites in the cytosols of cells from the senescent rats. Such analyses were performed in vitro at 0°C to eliminate metabolism of steroids. In addition, 3H dexamethasone was used instead of 3H cortisol to eliminate binding to plasma (or serum) transcortin. Inhibition of 3H uridine uptake requires specific glucocorticoid binding. The degree of inhibition at varying glucocorticoid dosages is proportional to the amount of specific binding to cytoplasmic macromolecules. Thus, age related reduction in specific glucocorticoid binding sites may be at least partially responsible for altered responsiveness of splenic leukocytes to these hormones.