{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:24:11Z","timestamp":1782260651173,"version":"3.54.5"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>Abnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has been invoked as a cause of secondary activation of the hypothalamic\u2013pituitary\u2013adrenal axis and hence androgen excess. However, this is based on urinary excretion of cortisol metabolites, which cannot detect tissue-specific changes in metabolism and may be confounded by obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess cortisol clearance and whole-body and tissue-specific activities of 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1 (HSD11B1)) in PCOS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Case\u2013control study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Medical center.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>A total of 20 overweight\u2013obese unmedicated Caucasian women with PCOS, aged 18\u201345 years, and 20 Caucasian controls matched for age, BMI, body fat distribution, and<jats:italic>HSD11B1<\/jats:italic>genotypes (rs846910 and rs12086634).<\/jats:p><\/jats:sec><jats:sec><jats:title>Main outcome measures<\/jats:title><jats:p>Cortisol metabolites were measured in 24\u200ah urine. During steady-state 9,11,12,12-[<jats:sup>2<\/jats:sup>H]<jats:sub>4<\/jats:sub>-cortisol infusion, cortisol clearance was calculated and whole-body HSD11B1 activity was assessed as the rate of appearance of 9,12,12-<jats:sup>2<\/jats:sup>H<jats:sub>3<\/jats:sub>-cortisol (d3-cortisol). Hepatic HSD11B1 activity was quantified as the generation of plasma cortisol following an oral dose of cortisone. Subcutaneous adipose HSD11B1 activity and<jats:italic>HSD11B1<\/jats:italic>mRNA were measured,<jats:italic>ex vivo<\/jats:italic>, in biopsies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Urinary cortisol metabolite excretion, deuterated cortisol clearance, and the rate of appearance of d3-cortisol did not differ between patients with PCOS and controls. However, hepatic HSD11B1 conversion of oral cortisone to cortisol was impaired (<jats:italic>P<\/jats:italic>&lt;0.05), whereas subcutaneous abdominal adipose tissue<jats:italic>HSD11B1<\/jats:italic>mRNA levels and activity were increased (<jats:italic>P<\/jats:italic>&lt;0.05) in women with PCOS when compared with controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Tissue-specific dysregulation of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased clearance of cortisol may result from obesity rather than PCOS.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-13-1030","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T12:14:35Z","timestamp":1397823275000},"page":"47-57","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":27,"title":["Tissue-specific dysregulation of 11\u03b2-hydroxysteroid dehydrogenase type 1 in overweight\/obese women with polycystic ovary syndrome compared with weight-matched controls"],"prefix":"10.1093","volume":"171","author":[{"given":"Alessandra","family":"Gambineri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flaminia","family":"Fanelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Tomassoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Munarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uberto","family":"Pagotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Andrew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Pasquali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"4","key":"1_11072351","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1210\/en.142.4.1371","volume":"142","author":"Seckl","year":"2001","journal-title":"Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0013-7227","issn-type":"print"},{"issue":"8","key":"2_18273241","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.2337\/diabetes.53.8.2051","volume":"53","author":"Basu","year":"2004","journal-title":"Diabetes","ISSN":"https:\/\/id.crossref.org\/issn\/0012-1797","issn-type":"print"},{"issue":"5549","key":"3_11436755","doi-asserted-by":"publisher","first-page":"2166","DOI":"10.1126\/science.1066285","volume":"294","author":"Masuzaki","year":"2001","journal-title":"Science","ISSN":"https:\/\/id.crossref.org\/issn\/0036-8075","issn-type":"print"},{"issue":"18","key":"4_19685951","doi-asserted-by":"publisher","first-page":"7088","DOI":"10.1073\/pnas.0305524101","volume":"101","year":"2004","journal-title":"PNAS","ISSN":"https:\/\/id.crossref.org\/issn\/0027-8424","issn-type":"print"},{"key":"5_19551124","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103676200","year":"2001","journal-title":"Journal of Biological Chemistry","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9258","issn-type":"print"},{"issue":"5","key":"6_6004197","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1210\/jc.83.5.1806","volume":"83","author":"Andrew","year":"1998","journal-title":"Journal of Clinical Endocrinology &amp; 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