Differential activation of adrenal steroid receptors in neural and immune tissues of Sprague Dawley, Fischer 344, and Lewis rats

Sprague Dawley (SD), Fischer 344 (F344), and Lewis (LEW) rats are used in a wide variety of laboratory studies. Compared to SD and LEW rats, F344 rats show significantly greater corticosterone secretion in response to stress, or to immune challenge. These strain differences in hypothalamic-pituitary-adrenal (HPA) axis responsivity have been the basis for many comparative studies investigating immunological and behavioural differences between the three strains. However, the effects of these strain differences in HPA axis responsivity have not been investigated at the level of adrenal steroid receptor activation in target tissues. The present study demonstrates that compared to SD and LEW rats, F344 rats exhibited a greater magnitude of Type II adrenal steroid receptor activation in brain tissues during stress. In contrast, Type II receptor activation in immune tissues of F344 rats following stress was similar to that of SD rats. Importantly, LEW rats exhibited the lowest magnitude of activation of Type II receptors in immune tissues during stress. No differences were observed between strains in the extent of stress-induced Type I adrenal steroid receptor activation. The observed differences between strains in corticosteroid-binding globulin (CBG) levels in plasma, pituitary, and immune tissue may mediate the differential access of corticosterone to neural versus immune tissues. These results indicate that strain differences in corticosterone secretion are manifested by differences in Type II receptor activation in neural as well as immune tissues. Moreover, they suggest that increased access of corticosterone to adrenal steroid receptors in brain areas of F344 rats may contribute to behavioural differences between strains, whereas decreased access of hormone to receptors in immune tissues of LEW rats may contribute to strain differences in susceptibility to autoimmune disease.