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

11 P-hydroxy steroid dehydrogenase type 1 (11 P-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 11β-HSD-1 in the hippocampus, producing suggestions that it may attenuate the deleterious effects of chronic glucocorticoid excess. However, 11β-HSD-1 predominantly catalyses 11 P-reduction in the intact liver and hippocampal cells, thus regenerating active glucocorticoids from inert substrate. We studied 11β-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-l activity (69 ± 9% of control), whereas Cortisol alone had no effect. In the liver, both chronic stress and Cortisol administration decreased 11β-HSD-1 activity (47 ± 11% and 49 ± 4% fall, resp.). Attenu...