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  Mono-allelic expression of the IGF-I receptor does not affect IGF responses in human fibroblasts

Hammer, E., Kutsche, K., Haag, F., Ullrich, K., Sudbrak, R., Willig, R. P., et al. (2004). Mono-allelic expression of the IGF-I receptor does not affect IGF responses in human fibroblasts. European Journal of Endocrinology, 151(4), 521-529. doi:10.1530/eje.0.1510521.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-87B5-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-87B6-E
Genre: Journal Article
Alternative Title : Eur J Endocrinol

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 Creators:
Hammer, E., Author
Kutsche, K., Author
Haag, F., Author
Ullrich, K., Author
Sudbrak, R.1, Author              
Willig, R. P., Author
Braulke, T., Author
Kubler, B., Author
Affiliations:
1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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 Abstract: OBJECTIVE: It has been suggested that mono-allelic deletion of the IGF-I receptor gene is causally related to severe intrauterine and postnatal growth deficiency whereas no IGF-I resistance was observed in the patients' fibroblasts. The expression and regulation of the growth-modulating IGF binding proteins (IGFBPs) have been investigated in serum and fibroblasts of a short girl with mono-allelic loss of the distal long arm of chromosome 15 (15q26.1-qter). PATIENT AND METHODS: The mono-allelic loss of the IGF-I receptor (IGF1R) gene was confirmed in a child with prenatal and severe postnatal growth retardation by fluorescence in situ hybridization, and was evaluated on the protein level in fibroblasts of the patient by FACS analysis and IGF cross-linkage. Additionally, expression of IGFBPs and cell-mediated degradation of IGFBP-3 were examined in the patient's fibroblasts. RESULTS: Levels of GH, IGF-I, and IGFBP-3 were above the 95th percentile in the serum of the 3-year-old girl with a mono-allelic deletion of the IGF1R gene, suggesting IGF-I resistance. In the patient's fibroblasts the IGF-I receptor concentration was half that in control cells. Whereas the pattern of secreted IGFBPs in response to IGFs was not altered, the abundance of secreted IGFBPs was higher in the patient's cells than in controls. Moreover, fibroblast-mediated degradation of 125I-labeled IGFBP-3 appears to be reduced in the patient's fibroblasts. The higher abundance of IGFBPs in the patient's fibroblasts might be responsible for the lack of IGF-I-stimulated [alpha-1-14C]methylaminoisobutyric acid transport. CONCLUSION: Our results suggest that the expression and regulation of IGFBPs in tissues from patients with mono-allelic deletion of the IGF-I receptor gene may lead to IGF sequestration and contribute to IGF-I resistance and growth retardation.

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Language(s): eng - English
 Dates: 2004-10
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: eDoc: 230217
DOI: 10.1530/eje.0.1510521
 Degree: -

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Title: European Journal of Endocrinology
  Alternative Title : Eur J Endocrinol
Source Genre: Journal
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Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 151 (4) Sequence Number: - Start / End Page: 521 - 529 Identifier: ISSN: 0804-4643