Clinical Endocrinology

Modulation of IGF-I receptors by exogenous hGH treatment in constitutionally short children

Authors

  • R. Eshet,

    1. Institute of Pediatric and Adolescent Endocrinology, Children's Medical Center of Israel, Beilinson Campus, Sackler Faculty of Medicine, Tel Aviv University, Israel
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  • B. Klinger,

    1. Institute of Pediatric and Adolescent Endocrinology, Children's Medical Center of Israel, Beilinson Campus, Sackler Faculty of Medicine, Tel Aviv University, Israel
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  • A. Silbergeld,

    1. Institute of Pediatric and Adolescent Endocrinology, Children's Medical Center of Israel, Beilinson Campus, Sackler Faculty of Medicine, Tel Aviv University, Israel
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  • Z. Laron

    Corresponding author
    1. Institute of Pediatric and Adolescent Endocrinology, Children's Medical Center of Israel, Beilinson Campus, Sackler Faculty of Medicine, Tel Aviv University, Israel
      Professor Z. Laron, Institute of Pediatric and Adolescent Endocrinology, Children's Medical Center of Israel, Beilinson Campus, Petah Tikva 49100, Israel. Fax: 972 9393930.
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Professor Z. Laron, Institute of Pediatric and Adolescent Endocrinology, Children's Medical Center of Israel, Beilinson Campus, Petah Tikva 49100, Israel. Fax: 972 9393930.

Summary

OBJECTIVE To study the in-vivo regulation of IGF-I binding sites on erythrocytes (RBC) following administration of growth hormone (hGH) to constitutionally short children. Recently, owing to biosynthetic techniques, treatment with hGH has been administered not only to children with GH deficiency but also to children with constitutional growth delay and with familiaf short stature.

PATIENTS AND DESIGN Growth hormone (rhGH-Norditropin, Novo/Nordisk) was administered at a dose of 0 1 U/kg/ day s.c. to 11 children with constitutional short stature. Before and at 1–2 months after initiation of treatment IGF-I binding sites and serum IGF-I were determined. Erythrocytes were separated from whole blood by centrifugation over Ficoll Hypaque and used to assess IGF-I binding sites.

RESULTS Serum IGF-I levels increased from 14 93 ±1 50 nmoI/I (mean±SEM) to 30 29 ±2 32 nmoI/I, with a mean difference of 15 38 + 2 21 (P= 0 00001). Concomitantly, the number of binding sites per cell decreased from 5 77 ±0.81 sites per celt (m±SEM) to 2 10 ±0 36, with a mean difference of - 3 67 ± 0 76 (P= 0.0003). The dissociation constant (Kd) also decreased from 0 47±016 MM (m±SEM) to 0.10±0 02 with a mean difference of 0 37±0.16 (P=0.02), indicating an increase in the affinity of the receptors.

CONCLUSION Treatment of children with constitutional short stature with hGH raises the circulating IGF-I levels and down-regulates the IGF-I receptors: This study shows that IGF-I is capable of regulating its homologous receptor concentrations in vivo and it is suggested that the measurement of IGF-I binding sites on RBC may be used for the diagnosis of subtle states of resistance to IGF-I.

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