Serum IGF-1 is insufficient to restore skeletal size in the total absence of the growth hormone receptor

Source: Wu Y et al J Bone Miner Res. 2013 Mar 3. doi: 10.1002/jbmr.1920.
Organisation: David B. Kriser Dental Center, Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY 10010; College of Integrative Medicine and Institute of Integrative Medicine, Dalian Medical University, Dalian, China.

growth hormone receptor insulin‑like growth factor 1 (.. growth hormone hormone somatomedin

States of growth hormone (GH) resistance, such those observed in Laron's dwarf patients, are characterized by mutations in the GH receptor (GHR), decreased serum and tissue IGF-1 levels, impaired glucose tolerance, and impaired skeletal acquisition. IGF-1 replacement therapy in such patients increases growth velocity but does not normalize growth. Herein we combined the GH-resistant (GHR knockout, GHRKO) mouse model with mice expressing the hepatic Igf-1 transgene (HIT) to generate the GHRKO-HIT mouse model. In GHRKO-HIT mice, serum IGF-1 levels were restored via transgenic expression of Igf-1, allowing us to study how endocrine IGF-1 affects growth, metabolic homeostasis, and skeletal integrity. We show that in a GH-resistant state, normalization of serum IGF-1 improved body adiposity and restored glucose tolerance but was insufficient to support normal skeletal growth, resulting in an osteopenic skeletal phenotype. The inability of serum IGF-1 to restore skeletal integrity in the total absence of GHR likely resulted from reduced skeletal Igf-1 gene expression, blunted GH-mediated effects on the skeleton that are independent of serum or tissue IGF-1, and from poor delivery of IGF-1 to the tissues. These findings are consistent with clinical data showing that IGF-I replacement therapy in patients with Laron's syndrome does not achieve full skeletal growth. (c) 2013 American Society for Bone and Mineral Research
Keywords:
MHDA- 2013/03/05 06:00    Medline  Literature Alert  Animal Model  Gene-Gene Link  Gene-Disease Link  
Relevant Pathways

This article mentions proteins present in the following molecular pathways (click to explore):

 Adipogenesis
 Micrornas In Cardiomyocyte Hyp..
 Synthesis, Secretion, And Deac..
 The IGF‑1 Receptor And Longevi..
 Regulation Of EIF‑4e And P70s6..
 Akt Signaling Pathway
 Growth Hormone Signaling Pathw..
 Multiple Antiapoptotic Pathway..
 Focal Adhesion
 Mtor Signaling Pathway
 IGF‑1 Signaling Pathway
 Apoptosis
 Senescence And Autophagy
 Regulation Of Bad Phosphorylat..
 Skeletal Muscle Hypertrophy Is..
 Endochondral Ossification
 Trefoil Factors Initiate Mucos..


Other Topics Mentioned:

Glucose Intolerance



   abstracted provided by MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

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