RESTRAINT STRESS-INDUCED THYMIC INVOLUTION AND CELL APOPTOSIS ARE DEPENDENT ON ENDOGENOUS GLUCOCORTICOIDS

The aim of this study was to investigate the specific role of endogeno us glucocorticoids (GC)following restraint stress on thymic involution and apoptosis. Restraint stress has been reported to alter physiologi cal and behavioral responses in experimental animals. Exposure of mice to restraint stress led to involution of the thymus, to a decrease of the CD4+ 8+ thymocyte subset, and to fragmentation of thymic DNA. The role of endogeneous GC in restraint stress-induced changes in the thy mus was studied by three experimental approaches: surgical adrenalecto my, chemical adrenalectomy. and blocking of GC receptors by a specific type II receptor antagonist. In surgically-Adx mice, which lack; endo genous GC, the effects of restraint on the thymus were wholly abrogate d. Pretreatment of restrained mice with metyrapone (an 11 beta hydroxy lase inhibitor that specifically inhibits GC biosynthesis) had the sam e consequence, and blockage of GC receptors with the specific CC type II receptor antagonist RU-38486 attenuated the effects of the stressor . These findings indicate that CC are involved in the restraint-induce d effects on the thymus. (C) 1998 Elsevier Science B.V.