Age-related changes in glucocorticoid binding by rat splenic leukocytes: possible cause of altered adaptive responsiveness.
Splenic leukocytes of senescent rats (24-26 mo) exhibit a 60% reduction in cortisol-induced inhibition of 3-H-uridine uptake when compared to mature adult animals (12-14 mo). The degree of inhibition is directly proportional to cortisol dosage up to 2 X 10-6 M. Specific binding of physiological (nanomolar) concentrations of 3-H-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, 3-H-dexamethasone was used instead of 3-H-cortisol to eliminate binding to plasma (or serum) transcortin. Inhibition of 3-H-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.
D000220:Adaptation, Biological; D000375:Aging; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002474:Cell-Free System; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000378:metabolism*; D006854:Hydrocortisone / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface; D013154:Spleen / Q000378:metabolism*; D014316:Tritium
D005938:Glucocorticoids; D011956:Receptors, Cell Surface; D014316:Tritium; D003907:Dexamethasone; D006854:Hydrocortisone