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Cortisol Metabolism as a Regulator of the Tissue-Specific Glucocorticoid Action

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The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease

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Abstract

Glucocorticoids have a diverse array of functions affecting almost all tissues in the body. While circulating cortisol levels are under the control of the hypothalamo–pituitary–adrenal axis, within individual organs and tissues, a series of enzymes is able to metabolize, either inactivating or reactivating glucocorticoids to control their availability to bind and activate the glucocorticoid receptor. The most studied of these enzymes are the 11β-hydroxysteroid dehydrogenases (type 1 and type 2) and the A-ring reductases (5α-reductase type 1 and 2 and 5β-reductase). 11β-Hydroxysteroid dehydrogenase type 1 regenerates active glucocorticoid (cortisol) from inactive cortisone and thus amplifies local glucocorticoid action. In contrast, 11β-hydroxysteroid dehydrogenase type 2 and the A-ring reductases clear and inactivate glucocorticoids. All have tissue-specific patterns of expression and regulation and have been implicated in the pathogenesis of many diseases that are discussed as part of this chapter. In addition, 11β-hydroxysteroid dehydrogenases type 1 represents a novel therapeutic target and selective inhibitors that decease tissue-specific glucocorticoid levels have reached phase II clinical trials. The prereceptor regulation of glucocorticoid action is therefore not only of fundamental physiological and pathological importance, but continues to represent an area of intense scientific and therapeutic interest.

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Authors and Affiliations

  1. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

    Emilia Sbardella

  2. Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, Churchill Hospital, University of Oxford, Oxford, OX3 7LE, UK

    Emilia Sbardella & Jeremy W. Tomlinson Ph.D., F.R.C.P.

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  1. Emilia Sbardella
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Correspondence to Jeremy W. Tomlinson Ph.D., F.R.C.P. .

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  1. Division of Endocrinology, Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Eliza B. Geer

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Sbardella, E., Tomlinson, J.W. (2017). Cortisol Metabolism as a Regulator of the Tissue-Specific Glucocorticoid Action. In: Geer, E. (eds) The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-45950-9_14

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