Tissue- and temporal-specific regulation of 11β-hydroxysteroid dehydrogenase type 1 by glucocorticoids in vivo

11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD-1) catalyses the interconversion of active corticosterone and inert 11-dehydrocorticosterone. Short-term glucocorticoid excess upregulates 11 beta-HSD-1 in liver and hippocampus leading to suggestions that 11 beta-HSD-1 ameliorates the deleterious effects of glucocorticoid excess by its 11 beta-dehydrogenase activity. However the predominant activity of 11 beta-HSD-1 in vive is 11 beta-reduction, thus generating active glucocorticoid. We have re-examined the time-course of glucocorticoid regulation of 11 beta-HSD-1 in the liver, hippocampus and kidney of adult male rats in vivo. Sham operation markedly reduced 11 beta-HSD-1 mRNA expression in all tissues, and reduced 11 beta-HSD bioactivity in liver and hippocampus when compared to untouched controls. Adrenalectomy reduced 11 beta-HSD-1 expression in all tissues in the shortterm (7 days), followed by subsequent recovery of enzyme activity by 21 days in liver and hippocampus. Dexamethasone replacement of adrenalectomised rats attenuated the initial decrease in hepatic 11 beta-HSD-1 activity, but by 21 days dexamethasone reduced activity compared to control levels. Thus glucocorticoids regulate 11 beta-HSD-1 in a complex tissue- and temporal-specific manner. This pattern of regulation suggests glucocorticoids repress 11 beta-HSD-1 at least in the liver, a pattern of regulation more consistent with the evidence that 11 beta-HSD-1 is an 11 beta-reductase in vive. Operational stress per se down-regulates 11 beta-HSD-1 which has implications for interpretation and design of in vive studies of 11 beta-HSD-1. (C) 1999 Elsevier Science Ltd. All rights reserved.