Alterations of Cortisol Metabolism in Human Disorders

Hormone Research in Pædiatrics
P C White

Abstract

The interconversion of active and inactive corticosteroids - cortisol and cortisone, respectively, in humans - is modulated by isozymes of 11β-hydroxysteroid dehydrogenase (11-HSD). Studies of this process have provided crucial insights into glucocorticoid effects in a wide variety of tissues. The 11-HSD1 isozyme functions mainly as an oxoreductase (cortisone to cortisol) and is expressed at high levels in the liver and other glucocorticoid target tissues. Because it is required for full physiological effects of cortisol, it has emerged as a drug target for metabolic syndrome and type 2 diabetes. Mutations in the corresponding HSD11B1 gene, or in the H6PD gene encoding hexose-6-phosphate dehydrogenase (which supplies the NADPH required for the oxoreductase activity of 11-HSD1), cause apparent cortisone reductase deficiency, a rare syndrome of adrenocortical hyperactivity and hyperandrogenism. In contrast, the 11-HSD2 isozyme functions as a dehydrogenase (cortisol to cortisone) and is expressed mainly in mineralocorticoid target tissues, where it bars access of cortisol to the mineralocorticoid receptor. Mutations in the HSD11B2 gene encoding 11-HSD2 cause the syndrome of apparent mineralocorticoid excess, a severe form of famil...Continue Reading

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Citations

Oct 18, 2018·International Journal of Tryptophan Research : IJTR·Adrian C Williams, Lisa J Hill
May 22, 2020·The Journal of Clinical Endocrinology and Metabolism·Anja Fenger DreyerMarianne Skovsager Andersen
Jul 22, 2020·Current Opinion in Pediatrics·Selma Feldman WitchelSharon E Oberfield
Jun 22, 2019·The Journal of Clinical Endocrinology and Metabolism·Géraldine VitelliusMarc Lombes
Dec 2, 2020·International Journal of Molecular Sciences·Magdalena MaciuszekMagdalena Chadzinska
Jun 3, 2021·International Journal of Molecular Sciences·Margaux LaulhéLaetitia Martinerie
Jul 13, 2021·The Journal of Sexual Medicine·Skyler HowellMohit Khera

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