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Increased insulin-like growth factor I binding to red blood cells of normal prepubertal children
A H Morris1, J L Joyce, E O Reiter
1Baystate Medical Center, Department of Pediatrics, Springfield, Massachusetts 01199.
Insights
Prepubertal children exhibit higher Insulin-like Growth Factor-I (IGF-I) binding to red blood cells than adults, potentially enhancing cellular response to lower IGF-I levels during growth. This difference is linked to increased receptor affinity, not number.
Area of Science:
- Endocrinology
- Pediatric Growth and Development
- Cellular Biology
Background:
- Circulating Insulin-like Growth Factor-I (IGF-I) levels in young children are often lower than in adults.
- Understanding IGF-I's role in growth is crucial, especially when circulating levels are low.
- Red blood cells offer a accessible model for studying IGF-I binding.
Purpose of the Study:
- To investigate differences in IGF-I binding to red blood cells between prepubertal children and adults.
- To explore the mechanisms behind any observed differences in IGF-I binding.
- To assess the potential implications for cellular responsiveness to IGF-I.
Main Methods:
- Studied binding of radiolabeled IGF-I (125I-Thr59-IGF-I) to red blood cells in 33 adults and 13 prepubertal children.
- Determined specific binding through dose-dependent displacement assays with unlabeled IGF-I and insulin.
- Utilized Scatchard analysis to evaluate receptor affinity and concentration.
Main Results:
- Prepubertal children showed significantly higher specific binding of 125I-Thr59-IGF-I to red blood cells compared to adults (p=0.01).
- Increased binding in children was attributed to higher receptor affinity (Ka), not receptor concentration.
- A positive correlation was found between specific binding and receptor affinity (p=0.007).
Conclusions:
- Prepubertal children have enhanced IGF-I binding to red blood cells, primarily due to increased receptor affinity.
- This enhanced binding may facilitate greater cellular responsiveness to lower circulating IGF-I levels during childhood growth.
- Red blood cell IGF-I binding could be a key factor in pediatric growth regulation.
Abstract:
Young children are growing at a time when circulating levels of IGF-I measured by RIA are generally less than or equal to values in nongrowing adults. 125I-Thr59-IGF-I binding to receptors on conveniently available red blood cells was studied in 33 normal adults (nine males, 24 females) and 13 normal prepubertal children aged 3-10 y (10 boys, three girls; all Tanner stage 1). Red blood cell specific binding of 125I-Thr59-IGF-I was determined by displacement of labeled Thr59-IGF-I by unlabeled Thr59-IGF-I or insulin in a dose-dependent manner. Mean (+/- SEM) 125I-Thr59-IGF-I specific binding was significantly higher (p = 0.01) in prepubertal children than in adults (13.9 +/- 0.7% versus 11.6 +/- 0.5%/3 x 10(9) cells/mL). Specific binding did not differ between adult males and females. There was no significant correlation between specific binding and reticulocyte count. Scatchard analysis demonstrated a linear plot. Increased binding to red blood cells in the prepubertal children appeared to be due to an increase in receptor affinity (Ka = 4.97 +/- 0.42 x 10(8) M-1 versus 3.70 +/- 0.41 x 10(8) M-1; children versus adults; p = 0.03). Mean receptor concentrations were not different in children and adults (64.4 +/- 8.5 versus 58.0 +/- 5.6 binding sites/cell). There was a significant positive correlation between 125I-Thr59-IGF-I specific binding and affinity (p = 0.007, r = 0.39). We speculate that the greater specific binding of labeled Thr59-IGF-I to red blood cells in prepubertal children may provide a mechanism for enhanced cellular responsiveness to relatively low levels of circulating IGF-I.