Attenuation of Hippocampal 11beta-Hydroxysteroid Dehydrogenase Type 1 by Chronic Psychosocial Stress in the Tree...

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) catalyses the interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone, thus regulating glucocorticoid access to intracellular receptors. In rats, chronic glucocorticoid excess or stress increases 11beta-HSD-1 in the hippocampus, producing suggestions that it may attenuate the deleterious effects of chronic glucocorticoid excess. However, 11beta-HSD-1 predominantly catalyses 11beta-reduction in the intact liver and hippocampal cells, thus regenerating active glucocorticoids from inert substrate. We studied 11beta-HSD activity in the tissues of male tree shrews following 28 days of sustained psychosocial stress or exogenous administration of cortisol. In the hippocampus, chronic psychosocial stress attenuated 11-HSD-1 activity (69 +/- 9% of control), whereas cortisol alone had no effect. In the liver, both chronic stress and cortisol administration decreased 11beta-HSD-1 activity (47 +/- 11% and 49 +/- 4% fall, resp.). Attenuation of 11beta-HSD-1 within tissues may reflect a homeostatic mechanism designed to minimise the adverse effects of prolonged stress and/or glucocorticoid excess.