Heath-Monnig E, Wohltmann H J, Mills-Dunlap B, Daughaday W H
J Clin Endocrinol Metab. 1987 Mar;64(3):501-7. doi: 10.1210/jcem-64-3-501.
Somatomedins are important mediators of GH action on skeletal tissues. A possible cause of growth failure, therefore, is impaired somatomedin (Sm) responsiveness of the target tissues. To investigate Sm responsiveness, we studied fibroblasts from 11 normal-statured individuals and 9 patients with short stature. Five of the short patients had normal serum GH and normal or increased Sm levels and, therefore, are considered possibly to be Sm resistant. The other short patients include 2 with Laron-type dwarfism and 2 with GH resistance of undefined type. As a measure of Sm responsiveness, we determined the ability of insulin-like growth factor I (IGF-I; Sm-C) to stimulate uptake of [3H]alpha-aminoisobutyric acid by fibroblasts. The mean ED50 of the 11 normal fibroblast cell lines was 3.2 +/- 0.9 (+/- SD) ng/ml. Fibroblasts from 8 of the 9 short-statured patients had ED50 values within the normal range. This included 2 fibroblast lines isolated from children with Laron-type dwarfism. Fibroblasts from 1 patient, however, were significantly less sensitive to IGF-I in 9 separate assays, with an ED50 of 10.7 +/- 1.8 ng/ml. Fibroblasts from the mother of the patient had an ED50 of 5.0 +/- 1.4 ng/ml, and fibroblasts from the father had an ED50 of 4.3 +/- 0.7 ng/ml, both above the normal mean. Measurements of [125I]IGF-I binding by suspended fibroblasts from this patient and her parents failed to demonstrate significant abnormalities in either the number of binding sites or the affinity of binding. We conclude that the ability of IGF-I to stimulate [3H]alpha-aminoisobutyric acid uptake by human fibroblasts provides a useful method of identifying short children with Sm resistance. Of five patients with clinical evidence of possible Sm resistance, fibroblasts from one consistently were hyporesponsive to IGF-I. Cells from two patients with Laron-type dwarfism were normally responsive to IGF-I.
生长调节素是生长激素作用于骨骼组织的重要介质。因此，生长发育迟缓的一个可能原因是靶组织对生长调节素（Sm）的反应性受损。为了研究Sm反应性，我们研究了11名身材正常个体和9名身材矮小患者的成纤维细胞。5名身材矮小患者的血清生长激素水平正常，Sm水平正常或升高，因此被认为可能存在Sm抵抗。其他身材矮小患者包括2例拉伦型侏儒症患者和2例不明类型的生长激素抵抗患者。作为Sm反应性的指标，我们测定了胰岛素样生长因子I（IGF-I；Sm-C）刺激成纤维细胞摄取[3H]α-氨基异丁酸的能力。11条正常成纤维细胞系的平均半数有效剂量（ED50）为3.2±0.9（±标准差）ng/ml。9名身材矮小患者中有8名的成纤维细胞ED50值在正常范围内。这包括从2例拉伦型侏儒症儿童分离得到的成纤维细胞系。然而，在9次独立试验中，1例患者的成纤维细胞对IGF-I的敏感性明显较低，ED50为10.7±1.8 ng/ml。该患者母亲的成纤维细胞ED50为5.0±1.4 ng/ml，父亲的成纤维细胞ED50为4.3±0.7 ng/ml，均高于正常平均值。对该患者及其父母的悬浮成纤维细胞进行[125I]IGF-I结合测定，未发现结合位点数量或结合亲和力有明显异常。我们得出结论，IGF-I刺激人成纤维细胞摄取[3H]α-氨基异丁酸的能力为识别存在Sm抵抗的矮小儿童提供了一种有用的方法。在5例有可能存在Sm抵抗临床证据的患者中，1例患者的成纤维细胞对IGF-I始终反应低下。2例拉伦型侏儒症患者的细胞对IGF-I反应正常。
