{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T20:31:40Z","timestamp":1764102700007,"version":"3.40.4"},"reference-count":49,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,12,1]]},"abstract":"<jats:p>The growth-promoting effect of combined therapy with GH and IGF-I in normal rats is not known. We therefore investigated the efficacy of treatment with recombinant human (rh)GH and\/or rhIGF-I on longitudinal bone growth and bone mass in intact, prepubertal, female Sprague-Dawley rats. rhGH was injected twice daily sc (5 mg\/kg\u00b7d) and rhIGF-I continuously infused sc (2.2 or 4.4 mg\/kg\u00b7d) for 28 days. Longitudinal bone growth was monitored by weekly x-rays of tibiae and nose-anus length measurements, and tibial growth plate histomorphology was analyzed. Bone mass was evaluated by peripheral quantitative computed tomography. In addition, serum levels of IGF-I, rat GH, acid labile subunit, IGF binding protein-3, 150-kDa ternary complex formation, and markers of bone formation and degradation were measured. Monotherapy with rhGH was more effective than rhIGF-I (4.4 mg\/kg\u00b7d) to increase tibia and nose-anus length, whereas combined therapy did not further increase tibia, or nose-anus, lengths or growth plate height. In contrast, combined rhGH and rhIGF-I (4.4 mg\/kg\u00b7d) therapy had an additive stimulatory effect on cortical bone mass vs rhGH alone. Combined treatment with rhGH and rhIGF-I resulted in markedly higher serum IGF-I concentrations vs rhGH alone but did not compromise the endogenous secretion of GH. We conclude that rhIGF-I treatment augments cortical bone mass but does not further improve bone growth in rhGH-treated young, intact, female rats.<\/jats:p>","DOI":"10.1210\/en.2014-1160","type":"journal-article","created":{"date-parts":[[2014,9,22]],"date-time":"2014-09-22T17:46:40Z","timestamp":1411408000000},"page":"4798-4807","source":"Crossref","is-referenced-by-count":15,"title":["Combined Treatment With GH and IGF-I: Additive Effect on Cortical Bone Mass But Not on Linear Bone Growth in Female Rats"],"prefix":"10.1210","volume":"155","author":[{"given":"Katja","family":"Sundstr\u00f6m","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology Unit (K.S., T.C., C.C.-H., L.S.), Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, SE-17176 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Therese","family":"Cedervall","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology Unit (K.S., T.C., C.C.-H., L.S.), Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, SE-17176 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claes","family":"Ohlsson","sequence":"first","affiliation":[{"name":"Centre for Bone and Arthritis Research (C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Camacho-H\u00fcbner","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology Unit (K.S., T.C., C.C.-H., L.S.), Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, SE-17176 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"S\u00e4vendahl","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology Unit (K.S., T.C., C.C.-H., L.S.), Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, SE-17176 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071612063988000_B1","first-page":"55","article-title":"Growth hormone and bone","volume":"19","author":"Ohlsson","year":"1998","journal-title":"Endocr Rev"},{"key":"2020071612063988000_B2","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1007\/s00467-008-1040-6","article-title":"Insulin-like growth factor-I and bone: lessons from mice and men","volume":"24","author":"Kawai","year":"2009","journal-title":"Pediatr Nephrol"},{"key":"2020071612063988000_B3","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/235107a0","article-title":"Somatomedin: proposed designation for sulphation factor","volume":"235","author":"Daughaday","year":"1972","journal-title":"Nature"},{"key":"2020071612063988000_B4","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1210\/er.2009-0010","article-title":"The role of liver-derived insulin-like growth factor-I","volume":"30","author":"Ohlsson","year":"2009","journal-title":"Endocr Rev"},{"key":"2020071612063988000_B5","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1677\/joe.0.1800247","article-title":"Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth","volume":"180","author":"Wang","year":"2004","journal-title":"J Endocrinol"},{"key":"2020071612063988000_B6","doi-asserted-by":"crossref","first-page":"4529","DOI":"10.1210\/jc.2007-0526","article-title":"The somatomedin hypothesis 2007: 50 years later","volume":"92","author":"Kaplan","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612063988000_B7","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1677\/joe.0.1620259","article-title":"Effects of IGF-I combined with GH on glucocorticoid-induced changes of bone and connective tissue turnover in man","volume":"162","author":"Berneis","year":"1999","journal-title":"J Endocrinol"},{"key":"2020071612063988000_B8","first-page":"2222","article-title":"Recombinant human insulin-like growth factor I, recombinant human growth hormone, and sex steroids: effects on markers of bone turnover in humans","volume":"81","author":"Mauras","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612063988000_B9","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1002\/jbmr.5650100912","article-title":"Treatment with growth hormone and IGF-I in growing rats increases bone mineral content but not bone mineral density","volume":"10","author":"Rosen","year":"1995","journal-title":"J Bone Miner Res"},{"key":"2020071612063988000_B10","first-page":"26","article-title":"rhGH\/rhIGF-1 co-administration versus rhGH alone in short, prepubertal children with low IGF-1 and normal stimulated GH levels: first-year results from a phase II, randomized, open-label, active-treatment controlled trial. 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Int"},{"key":"2020071612063988000_B17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0022-1759(01)00335-0","article-title":"Monoclonal anti-acid-labile subunit oligopeptide antibodies and their use in a two-site immunoassay for ALS measurement in humans","volume":"252","author":"Stadler","year":"2001","journal-title":"J Immunol Methods"},{"key":"2020071612063988000_B18","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0014-2999(86)90093-2","article-title":"Insulin-like growth factor I stimulates growth in normal growing rats","volume":"125","author":"Hizuka","year":"1986","journal-title":"Eur J Pharmacol"},{"key":"2020071612063988000_B19","first-page":"349","article-title":"A longitudinal study of the growth of the black-hooded rat: methods of measurement and rates of growth for skull, limbs, pelvis, nose-rump and tail lengths","volume":"106","author":"Hughes","year":"1970","journal-title":"J 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consequences","volume":"120","author":"Groesbeck","year":"1987","journal-title":"Endocrinology"},{"key":"2020071612063988000_B35","first-page":"375","article-title":"Morphological changes to somatotroph cells and in vitro individual GH release, in male rats treated with recombinant human GH","volume":"15","author":"Jim\u00e9nez-Reina","year":"2000","journal-title":"Histol Histopathol"},{"key":"2020071612063988000_B36","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.3181\/00379727-122-31384","article-title":"Influence of exogenous growth hormone on endogenous growth hormone release","volume":"122","author":"M\u00fcller","year":"1966","journal-title":"Proc Soc Exp Biol Med"},{"key":"2020071612063988000_B37","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1007\/BF03346893","article-title":"Effects of GH and IGF-I administration on GHRH and somatostatin mRNA levels: I. 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