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| GROWTH-HORMONE RESISTANCE AND INHIBITION OF SOMATOMEDIN ACTIVITY BY EXCESS OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEIN IN UREMIA |
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| Author(s): BLUM WF, RANKE MB, KIETZMANN K, TONSHOFF B, MEHLS O |
| Source: PEDIATRIC NEPHROLOGY Volume: 5 Issue: 4 Pages: 539-544 Published: 1991 |
| Times Cited: 177 References: 0 |
| 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 cross-linking 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: BLUM, WF (reprint author), UNIV TUBINGEN, KINDER KLIN, RUMELINSTR 23, W-7400 TUBINGEN 1, GERMANY |
| Publisher: SPRINGER VERLAG, 175 FIFTH AVE, NEW YORK, NY 10010 |
| Subject Category: Pediatrics; Urology & Nephrology |
| IDS Number: FW264 |
| ISSN: 0931-041X |
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