{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:15:22Z","timestamp":1761894922484},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2009,9,1]],"date-time":"2009-09-01T00:00:00Z","timestamp":1251763200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.bioscientifica.com\/journals\/reuselicenceeje\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Evidence from long-term clinical studies measuring urinary steroid ratios, and from<jats:italic>in vitro<\/jats:italic>studies, suggests that GH administered for longer than 2 months down-regulates 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1), thereby reducing cortisol regeneration in liver and adipose tissue. We aimed to measure acute effects of GH on 11\u03b2-HSD1 in liver and adipose tissue<jats:italic>in vivo<\/jats:italic>, including using a stable isotope tracer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Observational studies of GH withdrawal and reintroduction in patients with hypopituitarism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twelve men with benign pituitary disease causing GH and ACTH deficiency on stable replacement therapy for &gt;6 months were studied after GH withdrawal for 3 weeks, and after either placebo or GH injections were reintroduced for another 3 weeks. We measured cortisol kinetics during 9,11,12,12-<jats:sup>2<\/jats:sup>H<jats:sub>4<\/jats:sub>-cortisol (d4-cortisol) infusion, urinary cortisol\/cortisone metabolite ratios, liver 11\u03b2-HSD1 by appearance of plasma cortisol after oral cortisone, and 11\u03b2-HSD1 mRNA levels in subcutaneous adipose biopsies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GH withdrawal and reintroduction had no effect on 9,12,12-[<jats:sup>2<\/jats:sup>H]<jats:sub>3<\/jats:sub>-cortisol (d3-cortisol) appearance, urinary cortisol\/cortisone metabolite ratios, initial appearance of cortisol after oral cortisone, or adipose 11\u03b2-HSD1 mRNA. GH withdrawal increased plasma cortisol 30\u2013180\u200amin after oral cortisone, increased d4-cortisol clearance, and decreased relative excretion of 5\u03b1-reduced cortisol metabolites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this setting, GH did not regulate 11\u03b2-HSD1 rapidly<jats:italic>in vivo<\/jats:italic>in humans. Altered cortisol metabolism with longer term changes in GH may reflect indirect effects on 11\u03b2-HSD1. These data do not suggest that glucocorticoid replacement doses need to be increased immediately after introducing GH therapy to compensate for reduced 11\u03b2-HSD1 activity, although dose adjustment may be required in the longer term.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-09-0315","type":"journal-article","created":{"date-parts":[[2009,6,24]],"date-time":"2009-06-24T02:36:20Z","timestamp":1245810980000},"page":"375-380","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":5,"title":["Lack of regulation of 11\u03b2-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism"],"prefix":"10.1093","volume":"161","author":[{"given":"Helga A","family":"Sigurjonsdottir","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"Andrew","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland H","family":"Stimson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gudmundur","family":"Johannsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian R","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"issue":"5","key":"1_15737644","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/j.1365-2265.1994.tb01830.x","volume":"41","author":"Weaver","year":"1994","journal-title":"Clinical endocrinology","ISSN":"http:\/\/id.crossref.org\/issn\/0300-0664","issn-type":"print"},{"issue":"11","key":"2_6368878","doi-asserted-by":"publisher","first-page":"4172","DOI":"10.1210\/jc.84.11.4172","volume":"84","author":"Moore","year":"1999","journal-title":"Journal of Clinical Endocrinology &amp; 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