{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:11:49Z","timestamp":1793293909028,"version":"4.5.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2002,6,1]],"date-time":"2002-06-01T00:00:00Z","timestamp":1022889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The risk of glucocorticoid-induced osteoporosis increases substantially with age but there is considerable individual variation. In recent studies we have shown that the effects of glucocorticoids on bone are dependent on autocrine actions of the enzyme 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1); expression of 11\u03b2-HSD1 in osteoblasts (OBs) facilitates local synthesis of active glucocorticoids with consequent effects on osteoblastic proliferation and differentiation. Using primary cultures of human OBs, we have now characterized the age-specific variation in osteoblastic 11\u03b2-HSD1 and defined enzyme kinetics and regulation using natural and therapeutic glucocorticoids. 11\u03b2-HSD1 reductase activity (cortisone to cortisol conversion) was recognized in all OB cultures and correlated positively with age (r = 0.58 with all cultures, p &amp;lt; 0.01, and n = 18; r = 0.87 with calcaneal-derived cultures, p &amp;lt; 0.001, and n = 14). Glucocorticoid treatment caused a time- and dose-dependent increase in 11\u03b2-HSD1 activity over control (e.g., dexamethasone [DEX; 1 \u03bcM], 2.6-fold \u00b1 0.5 (mean \u00b1 SE), p &amp;lt; 0.001, and n = 16; cortisol (100 nM), 1.7-fold \u00b1 0.1, p &amp;lt; 0.05, and n = 14). Similar increases in 11\u03b2-HSD1 mRNA expression were indicated using real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) analyses (3.5-fold with DEX, p &amp;lt; 0.01; 2.5-fold with cortisol, p &amp;lt; 0.05). The capacity of 11\u03b2-HSD1 to metabolize the synthetic glucocorticoids prednisone and prednisolone was investigated in human OBs (hOBs) and fetal kidney-293 cells stably transfected with human 11\u03b2-HSD1 cDNA. Transfected cells and hOBs were able to interconvert prednisone and prednisolone with reaction kinetics indistinguishable from those for cortisone and cortisol. To assess the in vivo availability of substrates for osteoblastic 11\u03b2-HSD1, plasma cortisone and prednisone levels were measured in normal males before and after oral prednisolone (5 mg). The 9:00 a.m. serum cortisone levels were 110 \u00b1 5 nmol\/liter and prednisone levels peaked at 78 \u00b1 23 nmol\/liter 120 minutes after administration of prednisolone. Thus, therapeutic use of steroids increases substrate availability for 11\u03b2-HSD1 in bone. These studies indicate that activation of glucocorticoids at an autocrine level within bone is likely to play an important role in the age-related decrease in bone formation and increased risk of glucocorticoid-induced osteoporosis.<\/jats:p>","DOI":"10.1359\/jbmr.2002.17.6.979","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T21:01:19Z","timestamp":1146085279000},"page":"979-986","source":"Crossref","is-referenced-by-count":171,"title":["Osteoblastic 11\u03b2-Hydroxysteroid Dehydrogenase Type 1 Activity Increases With Age and Glucocorticoid Exposure"],"prefix":"10.1093","volume":"17","author":[{"given":"Mark S.","family":"Cooper","sequence":"first","affiliation":[{"name":"Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth H.","family":"Rabbitt","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa E.","family":"Goddard","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Immunology, Birmingham Heartlands and Solihull NHS Trust, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Bartlett","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Immunology, Birmingham Heartlands and Solihull NHS Trust, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hewison","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,10,27]]},"reference":[{"key":"2024013019082878400_bib1","first-page":"3441","article-title":"Clinical review 83: Mechanisms of glucocorticoid action in bone: Implications to glucocorticoid-induced osteoporosis","volume":"81","author":"Canalis","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013019082878400_bib2","first-page":"115","article-title":"Birth and death of bone cells: Basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis","volume":"21","author":"Manolagas","year":"2000","journal-title":"Endocr Rev"},{"key":"2024013019082878400_bib3","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1210\/endo.140.10.7034","article-title":"Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: Potential paracrine mechanisms of glucocorticoid-induced osteoporosis","volume":"140","author":"Hofbauer","year":"1999","journal-title":"Endocrinology"},{"key":"2024013019082878400_bib4","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1359\/jbmr.2001.16.1.97","article-title":"Comparison of trabecular bone microarchitecture and remodeling in glucocorticoid-induced and postmenopausal osteoporosis","volume":"16","author":"Carbonare","year":"2001","journal-title":"J Bone Miner Res"},{"key":"2024013019082878400_bib5","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1359\/jbmr.2000.15.6.993","article-title":"Use of oral corticosteroids and risk of fractures","volume":"15","author":"van Staa","year":"2000","journal-title":"J Bone Miner Res"},{"key":"2024013019082878400_bib6","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1056\/NEJM199708073370603","article-title":"Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis","volume":"337","author":"Adachi","year":"1997","journal-title":"N Engl J Med"},{"key":"2024013019082878400_bib7","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1056\/NEJM199807303390502","article-title":"Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. 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