Linked Life Data

20928887

Source:http://linkedlifedata.com/resource/pubmed/id/20928887

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-3-24
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1523-4681
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 American Society for Bone and Mineral Research.
pubmed:issnType
Electronic
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
761-8
pubmed:meshHeading
pubmed-meshheading:20928887-Adipose Tissue, pubmed-meshheading:20928887-Animals, pubmed-meshheading:20928887-Body Composition, pubmed-meshheading:20928887-Body Weight, pubmed-meshheading:20928887-Bone Development, pubmed-meshheading:20928887-Carrier Proteins, pubmed-meshheading:20928887-Femur, pubmed-meshheading:20928887-Gene Expression, pubmed-meshheading:20928887-Glycoproteins, pubmed-meshheading:20928887-Growth Hormone, pubmed-meshheading:20928887-Human Growth Hormone, pubmed-meshheading:20928887-Insulin-Like Growth Factor I, pubmed-meshheading:20928887-Liver, pubmed-meshheading:20928887-Male, pubmed-meshheading:20928887-Mechanical Processes, pubmed-meshheading:20928887-Mice, pubmed-meshheading:20928887-Mice, Inbred Strains, pubmed-meshheading:20928887-Mice, Transgenic, pubmed-meshheading:20928887-Osteocalcin, pubmed-meshheading:20928887-Osteogenesis, pubmed-meshheading:20928887-Puberty
pubmed:year
2011
pubmed:articleTitle
Growth hormone mediates pubertal skeletal development independent of hepatic IGF-1 production.
pubmed:affiliation
Division of Endocrinology, Diabetes and Bone Diseases, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural