Cargando…

Elevated Serum Levels of IGF-1 Are Sufficient to Establish Normal Body Size and Skeletal Properties Even in the Absence of Tissue IGF-1

Use of recombinant insulin-like growth factor 1 (IGF-1) as a treatment for primary IGF-1 deficiency in children has become increasingly common. When untreated, primary IGF-1 deficiency may lead to a range of metabolic disorders, including lipid abnormalities, insulin resistance, and decreased bone d...

Descripción completa

Detalles Bibliográficos
Autores principales: Elis, Sebastien, Courtland, Hayden-William, Wu, Yingjie, Rosen, Clifford J, Sun, Hui, Jepsen, Karl J, Majeska, Robert J, Yakar, Shoshana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wiley Subscription Services, Inc., A Wiley Company 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153133/
https://www.ncbi.nlm.nih.gov/pubmed/20200935
http://dx.doi.org/10.1002/jbmr.20
_version_ 1782209847985438720
author Elis, Sebastien
Courtland, Hayden-William
Wu, Yingjie
Rosen, Clifford J
Sun, Hui
Jepsen, Karl J
Majeska, Robert J
Yakar, Shoshana
author_facet Elis, Sebastien
Courtland, Hayden-William
Wu, Yingjie
Rosen, Clifford J
Sun, Hui
Jepsen, Karl J
Majeska, Robert J
Yakar, Shoshana
author_sort Elis, Sebastien
collection PubMed
description Use of recombinant insulin-like growth factor 1 (IGF-1) as a treatment for primary IGF-1 deficiency in children has become increasingly common. When untreated, primary IGF-1 deficiency may lead to a range of metabolic disorders, including lipid abnormalities, insulin resistance, and decreased bone density. To date, results of this therapy are considered encouraging; however, our understanding of the role played by IGF-1 during development remains limited. Studies on long-term treatment with recombinant IGF-1 in both children and animals are few. Here, we used two novel transgenic mouse strains to test the long-term effects of elevated circulating IGF-1 on body size and skeletal development. Overexpression of the rat igf1 transgene in livers of mice with otherwise normal IGF-1 expression (HIT mice) resulted in approximately threefold increases in serum IGF-1 levels throughout growth, as well as greater body mass and enhanced skeletal size, architecture, and mechanical properties. When the igf1 transgene was overexpressed in livers of igf1 null mice (KO-HIT), the comparably elevated serum IGF-1 failed to overcome growth and skeletal deficiencies during neonatal and early postnatal growth. However, between 4 and 16 weeks of age, increased serum IGF-1 fully compensated for the absence of locally produced IGF-1 because body weights and lengths of KO-HIT mice became comparable with controls. Furthermore, micro-computed tomography (µCT) analysis revealed that early deficits in skeletal structure of KO-HIT mice were restored to control levels by adulthood. Our data indicate that in the absence of tissue igf1 gene expression, maintaining long-term elevations in serum IGF-1 is sufficient to establish normal body size, body composition, and both skeletal architecture and mechanical function. © 2010 American Society for Bone and Mineral Research.
format Online
Article
Text
id pubmed-3153133
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher Wiley Subscription Services, Inc., A Wiley Company
record_format MEDLINE/PubMed
spelling pubmed-31531332011-08-19 Elevated Serum Levels of IGF-1 Are Sufficient to Establish Normal Body Size and Skeletal Properties Even in the Absence of Tissue IGF-1 Elis, Sebastien Courtland, Hayden-William Wu, Yingjie Rosen, Clifford J Sun, Hui Jepsen, Karl J Majeska, Robert J Yakar, Shoshana J Bone Miner Res Original Article Use of recombinant insulin-like growth factor 1 (IGF-1) as a treatment for primary IGF-1 deficiency in children has become increasingly common. When untreated, primary IGF-1 deficiency may lead to a range of metabolic disorders, including lipid abnormalities, insulin resistance, and decreased bone density. To date, results of this therapy are considered encouraging; however, our understanding of the role played by IGF-1 during development remains limited. Studies on long-term treatment with recombinant IGF-1 in both children and animals are few. Here, we used two novel transgenic mouse strains to test the long-term effects of elevated circulating IGF-1 on body size and skeletal development. Overexpression of the rat igf1 transgene in livers of mice with otherwise normal IGF-1 expression (HIT mice) resulted in approximately threefold increases in serum IGF-1 levels throughout growth, as well as greater body mass and enhanced skeletal size, architecture, and mechanical properties. When the igf1 transgene was overexpressed in livers of igf1 null mice (KO-HIT), the comparably elevated serum IGF-1 failed to overcome growth and skeletal deficiencies during neonatal and early postnatal growth. However, between 4 and 16 weeks of age, increased serum IGF-1 fully compensated for the absence of locally produced IGF-1 because body weights and lengths of KO-HIT mice became comparable with controls. Furthermore, micro-computed tomography (µCT) analysis revealed that early deficits in skeletal structure of KO-HIT mice were restored to control levels by adulthood. Our data indicate that in the absence of tissue igf1 gene expression, maintaining long-term elevations in serum IGF-1 is sufficient to establish normal body size, body composition, and both skeletal architecture and mechanical function. © 2010 American Society for Bone and Mineral Research. Wiley Subscription Services, Inc., A Wiley Company 2010-06 2010-01-14 /pmc/articles/PMC3153133/ /pubmed/20200935 http://dx.doi.org/10.1002/jbmr.20 Text en Copyright © 2010 American Society for Bone and Mineral Research http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Original Article
Elis, Sebastien
Courtland, Hayden-William
Wu, Yingjie
Rosen, Clifford J
Sun, Hui
Jepsen, Karl J
Majeska, Robert J
Yakar, Shoshana
Elevated Serum Levels of IGF-1 Are Sufficient to Establish Normal Body Size and Skeletal Properties Even in the Absence of Tissue IGF-1
title Elevated Serum Levels of IGF-1 Are Sufficient to Establish Normal Body Size and Skeletal Properties Even in the Absence of Tissue IGF-1
title_full Elevated Serum Levels of IGF-1 Are Sufficient to Establish Normal Body Size and Skeletal Properties Even in the Absence of Tissue IGF-1
title_fullStr Elevated Serum Levels of IGF-1 Are Sufficient to Establish Normal Body Size and Skeletal Properties Even in the Absence of Tissue IGF-1
title_full_unstemmed Elevated Serum Levels of IGF-1 Are Sufficient to Establish Normal Body Size and Skeletal Properties Even in the Absence of Tissue IGF-1
title_short Elevated Serum Levels of IGF-1 Are Sufficient to Establish Normal Body Size and Skeletal Properties Even in the Absence of Tissue IGF-1
title_sort elevated serum levels of igf-1 are sufficient to establish normal body size and skeletal properties even in the absence of tissue igf-1
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153133/
https://www.ncbi.nlm.nih.gov/pubmed/20200935
http://dx.doi.org/10.1002/jbmr.20
work_keys_str_mv AT elissebastien elevatedserumlevelsofigf1aresufficienttoestablishnormalbodysizeandskeletalpropertiesevenintheabsenceoftissueigf1
AT courtlandhaydenwilliam elevatedserumlevelsofigf1aresufficienttoestablishnormalbodysizeandskeletalpropertiesevenintheabsenceoftissueigf1
AT wuyingjie elevatedserumlevelsofigf1aresufficienttoestablishnormalbodysizeandskeletalpropertiesevenintheabsenceoftissueigf1
AT rosencliffordj elevatedserumlevelsofigf1aresufficienttoestablishnormalbodysizeandskeletalpropertiesevenintheabsenceoftissueigf1
AT sunhui elevatedserumlevelsofigf1aresufficienttoestablishnormalbodysizeandskeletalpropertiesevenintheabsenceoftissueigf1
AT jepsenkarlj elevatedserumlevelsofigf1aresufficienttoestablishnormalbodysizeandskeletalpropertiesevenintheabsenceoftissueigf1
AT majeskarobertj elevatedserumlevelsofigf1aresufficienttoestablishnormalbodysizeandskeletalpropertiesevenintheabsenceoftissueigf1
AT yakarshoshana elevatedserumlevelsofigf1aresufficienttoestablishnormalbodysizeandskeletalpropertiesevenintheabsenceoftissueigf1