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IGF Type 1 Receptor Ligand Binding Characteristics Are Altered in a Subgroup of Children with Intrauterine Growth Retardation

Laboratoire d’Explorations Fonctionnelles Endocriniennes, Hôpital d’Enfants Armand Trousseau, Assistance Publique des Hôpitaux de Paris (AP-HP), and INSERM, U-515, Hôpital Saint-Antoine, 75571 Paris, France

Address all correspondence and requests for reprints to: Prof. Yves Le Bouc, Laboratoire d’Explorations Fonctionnelles Endocriniennes, Hôpital Armand Trousseau, 26 avenue du Dr. Netter, 75571 Paris Cedex 12, France. E-mail: lebouc{at}st-antoine.inserm.fr

Abstract

The IGFs, IGF-I and IGF-II, regulate fetal growth by activating IGF type 1 receptors (IGF-IR). We aimed to quantify the binding of IGF-I to its cognate receptors in intrauterine growth-retarded children (IUGR). We measured the affinity of the erythrocyte IGF-IR and the number of IGF-IR receptors in 17 children with retarded growth (mean height, -2.7 SD), normal levels of GH, and a history of idiopathic intrauterine growth retardation (height at birth, -10 to -2 SD; mean, -3.1 SD). These children had reduced receptor affinity (K_d = 0.47 nM; P < 0.01) and more receptors per cell [binding capacity (B_max) = 11.7 binding sites/cell; P < 0.05)] compared with control children (K_d = 0.32 nM; B_max = 7.8 binding sites/cell). Moreover, the distributions of K_d and B_max suggested that there were two groups of IUGR children. Group 1 included subjects with normal receptor binding function (K_d = 0.36 nM; B_max = 8.2 sites/cell) and normal levels of circulating IGF-I. Group 2 comprised children with low receptor affinity (K_d = 0.56 nM) and increased receptor number (B_max = 14.7 sites/cell). This group showed significantly decreased IGF-I levels (-2.1 SD; P < 0.01). We investigated these IGF-IR binding parameters in two additional groups of growth-retarded children (Turner syndrome and patients with chronic renal failure), in whom the IGF-I axis was not believed to be the primary cause, and found that K_d and B_max were normal or nearly normal. We also measured IGF-IR binding parameters in 4 Seckel syndrome patients with IUGR and severely retarded growth (mean height, -7.9 SD). Their receptor affinity was reduced, but not statistically different, from that in controls, and their receptor number was normal, whereas IGF-I levels were elevated. Our results suggest heterogeneous alterations in IGF-IR binding function in IUGR patients.

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