title: Measurement of insulin-like growth factor I (IGF-I) responsiveness of fibroblasts of children with short stature: identification of a patient with IGF-I resistance.
abstract: 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.
mesh_terms: D000621:Aminoisobutyric Acids / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D004351:Drug Resistance; D004392:Dwarfism / Q000503:physiopathology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D013002:Somatomedins / Q000494:pharmacology*
chemical_list: D000621:Aminoisobutyric Acids; D013002:Somatomedins; C100049:2-aminoisobutyric acid; D007334:Insulin-Like Growth Factor I