Ducos B, Cabrol S, Houang M, Perin L, Holzenberger M, Le Bouc Y
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.
J Clin Endocrinol Metab. 2001 Nov;86(11):5516-24. doi: 10.1210/jcem.86.11.7985.
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.
胰岛素样生长因子（IGFs），即IGF-I和IGF-II，通过激活1型胰岛素样生长因子受体（IGF-IR）来调节胎儿生长。我们旨在量化宫内生长迟缓儿童（IUGR）中IGF-I与其同源受体的结合情况。我们测量了17名生长迟缓儿童（平均身高，-2.7标准差）红细胞IGF-IR的亲和力以及IGF-IR受体数量，这些儿童生长激素水平正常，且有特发性宫内生长迟缓病史（出生时身高，-10至-2标准差；平均，-3.1标准差）。与对照儿童（Kd = 0.32 nM；Bmax = 7.8个结合位点/细胞）相比，这些儿童的受体亲和力降低（Kd = 0.47 nM；P < 0.01），且每个细胞的受体更多[结合能力（Bmax）= 11.7个结合位点/细胞；P < 0.05]。此外，Kd和Bmax的分布表明存在两组IUGR儿童。第1组包括受体结合功能正常（Kd = 0.36 nM；Bmax = 8.2个位点/细胞）且循环IGF-I水平正常的受试者。第2组包括受体亲和力低（Kd = 0.56 nM）且受体数量增加（Bmax = 14.7个位点/细胞）的儿童。该组显示IGF-I水平显著降低（-2.1标准差；P < 0.01）。我们在另外两组生长迟缓儿童（特纳综合征和慢性肾功能衰竭患者）中研究了这些IGF-IR结合参数，在这些儿童中IGF-I轴不被认为是主要病因，结果发现Kd和Bmax正常或接近正常。我们还测量了4名患有IUGR且生长严重迟缓（平均身高，-7.9标准差）的塞克尔综合征患者的IGF-IR结合参数。他们的受体亲和力降低，但与对照组相比无统计学差异，且受体数量正常，而IGF-I水平升高。我们的结果表明IUGR患者中IGF-IR结合功能存在异质性改变。
