Activation of thymocyte deoxyribonucleic acid degradation by endogenous glucocorticoids

Immature lymphocytes in the thymus gland are killed by treatment with exogenous glucocorticoids. This steroid-mediated lymphocytolysis is preceded by numerous alterations in lymphocyte metabolism, including a DNA-degrading process in which the genome is cleaved at internucleosomal intervals. To date, this process has only been characterized by treating lymphocytes in vitro with glucocorticoids or by exogenous treatment of whole animals with adrenal steroids. To determine whether thymocyte DNA degradation could be activated by endogenous glucocorticoids, 4-wk-old chicks were treated with porcine adrenocorticotropic hormone (ACTH). This procedure elevated serum corticosterone levels approximately 80-fold within 2 h of hormone treatment. Following ACTH administration, thymocyte DNA was isolated and analyzed by agarose gel electrophoresis. The ACTH activated a DNA-degrading process that generated internucleosomal fragments of DNA identical in size to those observed following exogenous treatment with synthetic or naturally occurring glucocorticoids. Furthermore, this response could be inhibited by the glucocorticoid antagonist RU486 (17 beta-hydroxy-11 beta, 4-dimethylaminophenyl-17 alpha-propynl-estra-4,9,diene-3-one), indicating that adrenal steroids activate this process via the glucocorticoid receptor. These results demonstrate that lymphocyte DNA degradation does not result solely from exogenous glucocorticoid treatment; moreover, endogenous glucocorticoids can mediate this process and may thereby play an important role in thymic gland function.