IGF type 1 receptor ligand binding characteristics are altered in a subgroup of children with intrauterine growth retardation

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 cognat e receptors in intrauterine growth-retarded children (IUGR). We measured th e 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 G H, and a history of idiopathic intrauterine growth retardation (height at b irth, -10 to -2 SD; mean, -3.1 SD). These children had reduced receptor aff inity (K-d = 0.47 nM; P < 0.01) and more receptors per cell (binding capaci ty (B-max) = 11.7 binding sites/cell; P < 0.05)] compared with control chil dren (Kd = 0.32 nM; B-max = 7.8 binding sites/cell). Moreover, the distribu tions of Kd and B-max suggested that there were two groups of IUGR children . Group 1 included subjects with normal receptor binding function (Kd = 0.3 6 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 increa sed receptor number (B-max. = 14.7 sites/cell). This group showed significa ntly decreased IGF-1 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 i n 4 Seckel syndrome patients with IUGR and severely retarded growth (mean h eight, -7.9 SD). Their receptor affinity was reduced, but not statistically different, from that in controls, and their receptor number was normal, wh ereas IGF-1 levels were elevated. Our results suggest heterogeneous alterat ions in IGF-IR binding function in IUGR patients.