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
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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