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11β-HSD1, Inflammation, Metabolic Disease and Age-related Cognitive (dys)Function

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Abstract

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an intracellular amplifier of glucocorticoid action. By converting intrinsically inert glucocorticoids (cortisone, 11-dehydrocorticosterone) into their active forms (cortisol, corticosterone), 11β-HSD1 increases glucocorticoid access to receptors. Glucocorticoid hormones modulate diverse physiological processes, linking circadian rhythms to food seeking, motivational and cognitive behaviours, as well as intermediary metabolism and immune responses. They are a key component of pathways that buffer the organism against stressful challenges. Here we review the part played in these processes by 11β-HSD1, and discuss the promise of inhibitors of 11β-HSD1 in alleviating disorders associated with cumulative stress.

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Acknowledgements

We would like to thank members of the Endocrinology Unit, QMRI, for many stimulating discussions on all aspects of glucocorticoid metabolism and action. Work in the authors’ laboratories is funded by grants from the Wellcome Trust, the Scottish Hospitals Endowments Research Trust, the Medical Research Council, the British Heart Foundation, the Leukaemia Research Fund and the European Union.

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Correspondence to Karen E. Chapman.

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Special issue article in honor of George Fink.

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Chapman, K.E., Seckl, J.R. 11β-HSD1, Inflammation, Metabolic Disease and Age-related Cognitive (dys)Function. Neurochem Res 33, 624–636 (2008). https://doi.org/10.1007/s11064-007-9504-9

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