Molecular mechanisms of glucocorticoid resistance in splenocytes of socially stressed male mice

Splenocytes from socially stressed male mice display functional glucocorticoid (GC) resistance, viz., the antiproliferative effects of GC on lipopolysaccharide (LPS)-stimulated splenocytes is absent. In this study, we investigated changes in the structure and function of the glucocorticoid receptor (GR) in socially stressed animals. Changes of GR at both DNA and RNA levels were excluded. Reduced GR function was restricted to macrophages (CD11b(+)) in association with impaired nuclear translocation of GR after GC stimulation. Consequently, GC failed to block the activation of NF-kappaB in these cells. Thus, impaired nuclear translocation of GR and the lack of transcriptional suppression of NF-kappaB by GC were identified as the molecular mechanisms responsible for the observed GC resistance in spleens of socially stressed mice. (C) 2003 Elsevier Science B.V. All rights reserved.