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Growth hormone resistance and inhibition of somatomedin activity by excess of insulin-like growth factor binding protein in uraemia

  • Endocrine Changes Original Article
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Abstract

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) were studied in children with end-stage renal failure (ESRF,n=31) and chronic renal failure (n=11) with residual glomerular filtration. Somatomedin bioactivity in patient sera was found to be decreased while IGF-I and IGF-II levels by radio-immunoassay (RIA) were normal. In contrast, IGFBP-1 and IGFBP-3 levels (measured by RIA) were markedly increased in uraemia. Excess IGFBP was shown to be able to bind IGF by determination of the free IGF binding capacity. Using high-performance liquid chromatography a shift of the IGFBP-3 profile to low molecular weight components could be demonstrated in ESRF. Affinity crosslinking experiments showed that these low molecular weight IGFBP-3 immunoreactive forms are biologically active. In normal urine only IGFBP-3 forms smaller than 60 kDa were detected with a major peak at 12–20 kDa. Removal of excessive IGFBP from patient sera by affinity chromatography on an IGF-II Sepharose column resulted in a significant increase in somatomedin bioactivity. Model calculations on the interaction of IGF and IGFBP using empirical data suggested a reduction of IGF secretion in uraemia by an order of magnitude. It is concluded: (1) that renal failure causes an accumulation of low molecular weight IGFBP, (2) that the resulting excess of IGFBP acts as a somatomedin inhibitor, and (3) that in uraemia there is a relative growth hormone resistance with respect to IGF production.

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Authors and Affiliations

  1. University Children's Hospital, Rümelinstrasse 23, W-7400, Tübingen, Federal Republic of Germany

    Werner F. Blum, Michael B. Ranke & Klaus Kietzmann

  2. University Children's Hospital, Heidelberg, Federal Republic of Germany

    Burkhardt Tönshoff & Otto Mehls

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  1. Werner F. Blum
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  2. Michael B. Ranke
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  3. Klaus Kietzmann
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  4. Burkhardt Tönshoff
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  5. Otto Mehls
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Blum, W.F., Ranke, M.B., Kietzmann, K. et al. Growth hormone resistance and inhibition of somatomedin activity by excess of insulin-like growth factor binding protein in uraemia. Pediatr Nephrol 5, 539–544 (1991). https://doi.org/10.1007/BF01453697

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  • DOI: https://doi.org/10.1007/BF01453697

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