title: IGF type 1 receptor ligand binding characteristics are altered in a subgroup of children with intrauterine growth retardation.
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 (Kd = 0.47 nM; P < 0.01) and more receptors per cell [binding capacity (Bmax) = 11.7 binding sites/cell; P < 0.05)] compared with control children (Kd = 0.32 nM; Bmax = 7.8 binding sites/cell). Moreover, the distributions of Kd and Bmax suggested that there were two groups of IUGR children. Group 1 included subjects with normal receptor binding function (Kd = 0.36 nM; Bmax = 8.2 sites/cell) and normal levels of circulating IGF-I. Group 2 comprised children with low receptor affinity (Kd = 0.56 nM) and increased receptor number (Bmax = 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 Kd and Bmax 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.
authors.affiliation: 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.
authors.forename: B
authors.initials: B
authors.lastname: Ducos
authors.forename: S
authors.initials: S
authors.lastname: Cabrol
authors.forename: M
authors.initials: M
authors.lastname: Houang
authors.forename: L
authors.initials: L
authors.lastname: Perin
authors.forename: M
authors.initials: M
authors.lastname: Holzenberger
authors.forename: Y
authors.initials: Y
authors.lastname: Le Bouc
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism; D005317:Fetal Growth Retardation / Q000378:metabolism*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D011863:Radioimmunoassay; D017526:Receptor, IGF Type 1 / Q000378:metabolism*
chemical_list: D007457:Iodine Radioisotopes; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1