{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:17:43Z","timestamp":1791281863705,"version":"4.1.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2010,5,27]],"date-time":"2010-05-27T00:00:00Z","timestamp":1274918400000},"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":[[2010,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Use of recombinant insulin-like growth factor 1 (IGF-1) as a treatment for primary IGF-1 deficiency in children has become increasingly common. When untreated, primary IGF-1 deficiency may lead to a range of metabolic disorders, including lipid abnormalities, insulin resistance, and decreased bone density. To date, results of this therapy are considered encouraging; however, our understanding of the role played by IGF-1 during development remains limited. Studies on long-term treatment with recombinant IGF-1 in both children and animals are few. Here, we used two novel transgenic mouse strains to test the long-term effects of elevated circulating IGF-1 on body size and skeletal development. Overexpression of the rat igf1 transgene in livers of mice with otherwise normal IGF-1 expression (HIT mice) resulted in approximately threefold increases in serum IGF-1 levels throughout growth, as well as greater body mass and enhanced skeletal size, architecture, and mechanical properties. When the igf1 transgene was overexpressed in livers of igf1 null mice (KO-HIT), the comparably elevated serum IGF-1 failed to overcome growth and skeletal deficiencies during neonatal and early postnatal growth. However, between 4 and 16 weeks of age, increased serum IGF-1 fully compensated for the absence of locally produced IGF-1 because body weights and lengths of KO-HIT mice became comparable with controls. Furthermore, micro-computed tomography (\u00b5CT) analysis revealed that early deficits in skeletal structure of KO-HIT mice were restored to control levels by adulthood. Our data indicate that in the absence of tissue igf1 gene expression, maintaining long-term elevations in serum IGF-1 is sufficient to establish normal body size, body composition, and both skeletal architecture and mechanical function. \u00a9 2010 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1002\/jbmr.20","type":"journal-article","created":{"date-parts":[[2010,2,1]],"date-time":"2010-02-01T11:40:50Z","timestamp":1265024450000},"page":"1257-1266","source":"Crossref","is-referenced-by-count":66,"title":["Elevated serum levels of IGF-1 are sufficient to establish normal body size and skeletal properties even in the absence of tissue IGF-1"],"prefix":"10.1093","volume":"25","author":[{"given":"Sebastien","family":"Elis","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayden-William","family":"Courtland","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford J","family":"Rosen","sequence":"additional","affiliation":[{"name":"Maine Medical Center Research Institute, Scarborough, ME, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl J","family":"Jepsen","sequence":"additional","affiliation":[{"name":"Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Majeska","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, City College of New York, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoshana","family":"Yakar","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,5,27]]},"reference":[{"key":"2024020320142979000_bib1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/0-387-26274-1_3","article-title":"Insulin-like growth factor 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