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The hypothalamo-pituitary-growth hormone insulin-like growth factor 1 axis in children with chronic renal failure
1Department of Paediatric Nephrology, Royal Free Hospital NHS Trust, London, England, United Kingdom.
Insights
Children with chronic renal failure (CRF) exhibit high growth hormone (GH) levels and altered GH regulation. Decreased GH binding protein (GHBP) and fragmented IGFBP3 in transplanted children may impact IGF1 bioactivity.
Area of Science:
- Pediatric Endocrinology
- Nephrology
- Growth Hormone Axis
Background:
- Children with chronic renal failure (CRF) often present with elevated growth hormone (GH) levels.
- Hypothalamic sensitivity to GH secretion modulators is increased in pediatric CRF.
- GH binding protein (GHBP) levels are reduced in CRF, suggesting diminished GH receptor activity.
Purpose of the Study:
- To investigate the status of GH, GHBP, and IGFBP3 in children with CRF and post-transplantation.
- To explore potential alterations in IGFBP3 integrity and their implications for IGF1 bioactivity.
Main Methods:
- Measurement of GH levels.
- Assessment of GH binding protein (GHBP) levels.
- Analysis of IGFBP3 by immunoradiometric assay and Western immunoblotting to detect intact forms and fragments.
Main Results:
- Elevated GH levels were observed in children with CRF.
- GHBP levels were decreased in CRF patients.
- While total IGFBP3 levels were normal by immunoradiometric assay, intact IGFBP3 was low in transplanted children, with an excess of smaller fragments detected by Western immunoblotting.
Conclusions:
- Altered GH dynamics and reduced GHBP are characteristic of pediatric CRF.
- The presence of IGFBP3 fragments in transplanted children may impair IGF1 bioactivity, warranting further investigation into growth disturbances.
Abstract:
Growth hormone (GH) levels are high in children with chronic renal failure (CRF), and there is increased hypothalamic sensitivity to the factors that normally modulate GH secretion. GH binding protein (GHBP) is decreased, which may reflect decreased GH receptor activity. IGFBP3 levels are normal in both CRF and transplanted children when measured by immunoradiometric assay, but intact IGFBP3 is low in transplanted children with an excess of small fragments, measured by Western immunoblotting. These fragments may interfere with IGF1 bioactivity.