Endocrine Abstracts

The presence of the enzymes of local metabolism of glucocorticoids in lymphoid organs and many other tissues suggests that the local glucocorticoid signal is not determined only by plasma level of glucocorticoids but also by the local activity of these enzymes. Using resident-intruder test the present study determined if chronic social stress modulates local metabolism of corticosterone and 11-dehydrocorticosterone in rats of Fisher 344 (F344) and Lewis (LEW) strains, which differ in their response to social stressors and inflammation. We demonstrated that social defeat significantly increased regeneration of corticosterone from 11-dehydrocorticosterone in thymus, spleen and mesenteric lymphatic nodes (MLN) but not pituitary of both strains. When compared with F344 strain, LEW rats showed lower corticosterone regeneration in pituitary of unstressed and stressed animals and higher corticosterone regeneration in thymic and MLN mobile cells after chronic stress. In contrast, stress-induced increase of corticosterone regeneration in stroma tissues of all lymphoid organs was similar in both strains. Social defeat was also associated with changes in expression of enzymes participating in local metabolism of glucocorticoids: 11β-hydroxysteroid dehydrogenase type 1 (11HSD1), 11β-hydroxysteroid dehydrogenase type 2 (11HSD2) and hexose-6-phosphate dehydrogenase (H6PDH). Whereas F344 rats exhibited significant upregulation of 11HSD1 mRNA, 11HSD2 mRNA and H6PDH mRNA expression in thymus and 11HSD1 mRNA in spleen, LEW rats showed an apparent insensitivity to stress in all lymphoid organs and neither of the transcripts was upregulated by stress. Our results indicate that social stress amplifies glucocorticoid regeneration in the lymphoid organs including the expression of genes involved in local metabolism of glucocorticoids and that this process is partly determined by the genetic background. The study was supported by Czech Science Foundation.