Artículo
Serum IGF-1 is insufficient to restore skeletal size in the total absence of the growth hormone receptor
Wu, Yingjie; Sun, Hui; Basta Pljakic, Jelena; Cardoso, Luis; Kennedy, Oran D.; Jasper, Hector Guillermo
; Domene, Horacio Mario
; Karabatas, Liliana Margarita
; Guida, María Clara
; Schaffler, Mitchell B.; Rosen, Clifford J.; Yakar, Shoshana
Fecha de publicación:
07/2013
Editorial:
Wiley
Revista:
Journal Of Bone And Mineral Research
ISSN:
1523-4681
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
States of growth hormone (GH) resistance, such those observed in Laron 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 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 syndrome does not achieve full skeletal growth.
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Articulos(CEDIE)
Articulos de CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Articulos de CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Citación
Wu, Yingjie; Sun, Hui; Basta Pljakic, Jelena; Cardoso, Luis; Kennedy, Oran D.; et al.; Serum IGF-1 is insufficient to restore skeletal size in the total absence of the growth hormone receptor; Wiley; Journal Of Bone And Mineral Research; 28; 7; 7-2013; 1575-1586
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