Growth hormone mediates pubertal skeletal development independent of hepatic IGF-1 production
Autor: | Mordechay Beth-On, Clifford J. Rosen, Sebastien Elis, Yingjie Wu, Hayden William Courtland, Shoshana Yakar, Hui Sun |
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Přispěvatelé: | Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Maine Medical Center Research Institute (MMCRI), Icahn School of Medicine at Mount Sinai, Partenaires INRAE, NIAMS (NIH) AR054919 AR055141 AR053853 |
Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
Male
Endocrinology Diabetes and Metabolism medicine.medical_treatment Adipose tissue Gene Expression mechanical properties bone Mice 0302 clinical medicine MICRO–COMPUTED TOMOGRAPHY Osteogenesis igf 1 Orthopedics and Sports Medicine Femur Insulin-Like Growth Factor I 0303 health sciences biology Human Growth Hormone micro computed tomography medicine.anatomical_structure Adipose Tissue Liver Osteocalcin IGF-1 Body Composition Original Article lid mice medicine.drug medicine.medical_specialty [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT] endocrine 030209 endocrinology & metabolism Mice Inbred Strains Mice Transgenic 03 medical and health sciences Paracrine signalling Internal medicine medicine Endocrine system Animals Autocrine signalling 030304 developmental biology Glycoproteins Mechanical Phenomena Bone Development business.industry Growth factor Body Weight Puberty Endocrinology Growth Hormone Pegvisomant biology.protein Cortical bone business Carrier Proteins |
Zdroj: | Journal of Bone and Mineral Research Journal of Bone and Mineral Research, American Society for Bone and Mineral Research, 2011, 26 (4), pp.761-768. ⟨10.1002/jbmr.265⟩ |
ISSN: | 0884-0431 |
Popis: | Deficiencies in either growth hormone (GH) or insulin-like growth factor 1 (IGF-1) are associated with reductions in bone size during growth in humans and animal models. Liver-specific IGF-1-deficient (LID) mice, which have 75% reductions in serum IGF-1, were created previously to separate the effects of endocrine (serum) IGF-1 from autocrine/paracrine IGF-1. However, LID mice also have two- to threefold increases in GH, and this may contribute to the observed pubertal skeletal phenotype. To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age. Treatment of LID mice with pegvisomant resulted in significant reductions in body weight, femur length (Le), and femur total area (Tt.Ar), as well as further reductions in serum IGF-1 levels by 8 weeks of age, compared with the mean values of vehicle-treated LID mice. Reductions in both Tt.Ar and Le were proportional after treatment with pegvisomant. On the other hand, the relative amount of cortical tissue formed (RCA) in LID mice treated with pegvisomant was significantly less than that in both vehicle-treated LID and control mice, indicating that antagonizing GH action, either directly (through GH receptor signaling inhibition) or indirectly (through further reductions in serum/tissue IGF-1 levels), results in disproportionate reductions in the amount of cortical bone formed. This resulted in bones with significantly reduced mechanical properties (femoral whole-bone stiffness and work to failure were markedly decreased), suggesting that compensatory increases of GH in states of IGF-1 deficiency (LID mice) act to protect against a severe inhibition of bone modeling during growth, which otherwise would result in bones that are too weak for normal and/or extreme loading conditions. © 2011 American Society for Bone and Mineral Research. |
Databáze: | OpenAIRE |
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