Glucocorticoid-mediated activation of DNA degradation in avian lymphocytes

Abstract

Little information is known about the molecular mechanism of programmed cell death in the avian species. In the current study we have analyzed this process in chickens using a glucocorticoid-lymphocyte model system. Three-week-old male broiler chicks were treated in vivo with the synthetic glucocorticoid, dexamethasone. Following this treatment genomic DNA was isolated from thymocytes and analyzed by agarose gel electrophoresis. Dexamethasone activated a DNA degrading process in which the genome was specifically cleaved at internucleosomal intervals. This steroid-induced response occurred prior to thymocyte cell death and was time and glucocorticoid dose dependent, as well as tissue and steroid specific. Only the glucocorticoid class of steroid hormones could elicit this response and DNA degradation was only detectable in lymphoid tissues that contained immature lymphocytes. Internucleosomal DNA degradation could also be elicited via administration of adrenocorticotrophic hormone, a treatment that elevates endogenous glucocorticoids. Based on these data, glucocorticoid-activated DNA degradation of the avian thymocyte genome appears to be a steroid receptor-mediated process which involves the activation of an endogenous nuclease that cleaves the genome at internucleosomal sites. Degradation of the thymocyte genome occurs prior to cell death and may represent an initial event in a cascade of hormone-mediated processes that culminate in a type of cellular suicide referred to as programmed cell death.