LONG-TERM CORTICOSTEROID TREATMENT BUT NOT CHRONIC STRESS AFFECTS 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-I ACTIVITY IN RAT-BRAIN AND PERIPHERAL-TISSUES

Long-term treatment (21 days) of male rats with corticosterone in the drinking water caused a significant increase in the activity of the NA DP-dependent form of 11 beta-hydroxysteroid dehydrogenase (11-HSD1) in the pituitary, thymus, and spleen, (marginally in the hippocampus, am ygdala and lymph nodes), without having any effect in a number of othe r central and peripheral tissues. In contrast, repeated restraint stre ss, although increasing plasma corticosterone to the same level as tha t observed after its administration, failed to change the activity of this key regulatory enzyme, which allows aldosterone to exert its spec ific effects in the presence of a large excess of corticosterone. This resistance to elevation in 11-HSD activity was also observed in the t hymuses of subordinate rats during social stratification in a visible burrow system. In both cases, the circulating levels of corticosterone were much higher in stressed rats than in control animals. Factors wh ich might account for these differences in response are discussed and compared with the situation in intact cells where, unlike in tissue ho mogenates, the reduction of 11-dehydrocorticosterone to corticosterone (reductase activity) appears to predominate. (C) 1997 Elsevier Scienc e Ltd.