{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T16:44:19Z","timestamp":1773420259885,"version":"3.50.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>Glucocorticoids are widely prescribed for their anti-inflammatory properties, but have \u2018Cushingoid\u2019 side effects including visceral obesity, muscle myopathy, hypertension, insulin resistance, type 2 diabetes mellitus, osteoporosis, and hepatic steatosis. These features are replicated in patients with much rarer endogenous glucocorticoid (GC) excess (Cushing\u2019s syndrome), which has devastating consequences if left untreated. Current medical therapeutic options that reverse the tissue-specific consequences of hypercortisolism are limited. In this article, we review the current evidence that local GC metabolism via the enzyme 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1) plays a central role in mediating the adverse metabolic complications associated with circulatory GC excess \u2013 challenging our current view that simple delivery of active GCs from the circulation represents the most important mode of GC action. Furthermore, we explore the potential for targeting this enzyme as a novel therapeutic strategy for the treatment of both endogenous and exogenous Cushing\u2019s syndrome.<\/jats:p>","DOI":"10.1530\/eje-15-1237","type":"journal-article","created":{"date-parts":[[2016,3,9]],"date-time":"2016-03-09T03:03:45Z","timestamp":1457492625000},"page":"R81-R87","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":29,"title":["MECHANISMS IN ENDOCRINOLOGY: Tissue-specific activation of cortisol in Cushing\u2019s syndrome"],"prefix":"10.1093","volume":"175","author":[{"given":"Stuart A","family":"Morgan","sequence":"first","affiliation":[{"name":"1Institute of Metabolism and Systems ResearchInstitute of Biomedical Research, University of Birmingham, Birmingham, UK"},{"name":"2Centre for Endocrinology Diabetes and MetabolismBirmingham Health Partners, University of Birmingham, Birmingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaki K","family":"Hassan-Smith","sequence":"additional","affiliation":[{"name":"1Institute of Metabolism and Systems ResearchInstitute of Biomedical Research, University of Birmingham, Birmingham, UK"},{"name":"2Centre for Endocrinology Diabetes and MetabolismBirmingham Health Partners, University of Birmingham, Birmingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth G","family":"Lavery","sequence":"additional","affiliation":[{"name":"1Institute of Metabolism and Systems ResearchInstitute of Biomedical Research, University of Birmingham, Birmingham, UK"},{"name":"2Centre for Endocrinology Diabetes and MetabolismBirmingham Health Partners, University of Birmingham, Birmingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"key":"2016070618583855000_175.2.R83.1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/qjmed\/93.2.105","article-title":"Use of oral corticosteroids in the United Kingdom","volume":"93","author":"van Staa","year":"2000","journal-title":"QJM: Monthly Journal of the Association of Physician"},{"key":"2016070618583855000_175.2.R83.2","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/acr.21796","article-title":"Prevalence of oral glucocorticoid usage in the United States: a general population perspective","volume":"65","author":"Overman","year":"2013","journal-title":"Arthritis Care & Research (Hoboken)"},{"key":"2016070618583855000_175.2.R83.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.07950.x"},{"key":"2016070618583855000_175.2.R83.4","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e4928"},{"key":"2016070618583855000_175.2.R83.5","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-141-10-200411160-00007"},{"key":"2016070618583855000_175.2.R83.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68699-6"},{"key":"2016070618583855000_175.2.R83.7","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/j.1550-8528.1994.tb00097.x","article-title":"The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). 1932","volume":"2","author":"Cushing","year":"1994","journal-title":"Obesity Research"},{"key":"2016070618583855000_175.2.R83.8","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2957"},{"key":"2016070618583855000_175.2.R83.9","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1942"},{"key":"2016070618583855000_175.2.R83.10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1323681111"},{"key":"2016070618583855000_175.2.R83.11","doi-asserted-by":"publisher","DOI":"10.1210\/en.135.6.2533"},{"key":"2016070618583855000_175.2.R83.12","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.4.1325"},{"key":"2016070618583855000_175.2.R83.13","doi-asserted-by":"publisher","DOI":"10.1210\/jc.87.3.1205"},{"key":"2016070618583855000_175.2.R83.14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.79.2.480"},{"key":"2016070618583855000_175.2.R83.15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.5.2305"},{"key":"2016070618583855000_175.2.R83.16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512635200"},{"key":"2016070618583855000_175.2.R83.17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.87.1.57"},{"key":"2016070618583855000_175.2.R83.18","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1507\/endocrj.K08E-008","article-title":"A case of cortisol producing adrenal adenoma without phenotype of Cushing\u2019s syndrome due to impaired 11beta-hydroxysteroid dehydrogenase 1 activity","volume":"55","author":"Arai","year":"2008","journal-title":"Endocrine Journal"},{"key":"2016070618583855000_175.2.R83.19","doi-asserted-by":"crossref","unstructured":"Lee MJ Fried SK Mundt SS Wang Y Sullivan S Stefanni A Daugherty BL Hermanowski-Vosatka A. Depot-specific regulation of the conversion of cortisone to cortisol in human adipose tissue. Obesity (Silver Spring) 2008 16 1178\u20131185. (doi:10.1038\/oby.2008.207)","DOI":"10.1038\/oby.2008.207"},{"key":"2016070618583855000_175.2.R83.20","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.1.151"},{"key":"2016070618583855000_175.2.R83.21","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-020687"},{"key":"2016070618583855000_175.2.R83.22","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2002.17.6.979"},{"key":"2016070618583855000_175.2.R83.23","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.257"},{"key":"2016070618583855000_175.2.R83.24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01465.x"},{"key":"2016070618583855000_175.2.R83.25","doi-asserted-by":"publisher","DOI":"10.1530\/eje.1.02228"},{"key":"2016070618583855000_175.2.R83.26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2005.02281.x"},{"key":"2016070618583855000_175.2.R83.27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0300372101"},{"key":"2016070618583855000_175.2.R83.28","doi-asserted-by":"publisher","DOI":"10.1124\/mol.62.2.297"},{"key":"2016070618583855000_175.2.R83.29","first-page":"2606","article-title":"BOL-303242-X, a novel selective glucocorticoid receptor agonist, with full anti-inflammatory properties in human ocular cells","volume":"15","author":"Zhang","year":"2009","journal-title":"Molecular Vision"},{"key":"2016070618583855000_175.2.R83.30","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1097\/MED.0b013e3283631809","article-title":"Update in the medical therapy of Cushing\u2019s disease","volume":"20","author":"Nieman","year":"2013","journal-title":"Current Opinion in Endocrinology, Diabetes and Obesity"},{"key":"2016070618583855000_175.2.R83.31","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3126"},{"key":"2016070618583855000_175.2.R83.32","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-009-0209-8"},{"key":"2016070618583855000_175.2.R83.33","doi-asserted-by":"publisher","DOI":"10.1021\/jm025530f"},{"key":"2016070618583855000_175.2.R83.34","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-002-0959-6"},{"key":"2016070618583855000_175.2.R83.35","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0344"},{"key":"2016070618583855000_175.2.R83.36","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050119"},{"key":"2016070618583855000_175.2.R83.37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2009.01034.x"},{"key":"2016070618583855000_175.2.R83.38","unstructured":"Hawkins M Hunter D Kishore P Schwartz S Hompesch M Hollis G Levy R Williams B Huber R. INCB013739, a Selective Inhibitor of 11\u03b2-Hydroxysteroid Dehydrogenase Type 1 (11\u03b2HSD1), Improves Insulin Sensitivity and Lower Plasma Cholesterol Over 28 Days in Patients with Type 2 Diabetes Mellitus. 68th Scientific session of the American Diabetes Association, San Francisco, CA, USA, 2008."},{"key":"2016070618583855000_175.2.R83.39","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-2315"},{"key":"2016070618583855000_175.2.R83.40","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01375.x"},{"key":"2016070618583855000_175.2.R83.41","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jash.2011.01.009","article-title":"Efficacy and safety of the selective 11beta-HSD-1 inhibitors MK-0736 and MK-0916 in overweight and obese patients with hypertension","volume":"5","author":"Shah","year":"2011","journal-title":"Journal of the American Society of Hypertension"},{"key":"2016070618583855000_175.2.R83.42","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010374470"},{"key":"2016070618583855000_175.2.R83.43","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-41-4-717"},{"key":"2016070618583855000_175.2.R83.44","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.12.7605"},{"key":"2016070618583855000_175.2.R83.45","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq149"},{"key":"2016070618583855000_175.2.R83.46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500641102"},{"key":"2016070618583855000_175.2.R83.47","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1398"},{"key":"2016070618583855000_175.2.R83.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2010.12.040"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/175\/2\/R83.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/175\/2\/R83.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:33:50Z","timestamp":1676392430000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/175\/2\/R81\/6655090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8]]},"references-count":48,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/eje-15-1237","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8]]}}}