Normal somatomedin-C/insulin-like growth factor I binding and action in cultured human fibroblasts from Turner syndrome.
Growth retardation is a major manifestation of Turner syndrome (TS). Since plasma growth hormone and somatomedin-C/insulin-like growth factor I (SM-C/IGF-I) levels are generally normal, growth failure has been ascribed to peripheral defects in SM-C/IGF-I receptors or action. We have measured the binding of [125I]SM-C/IGF-I to cultured fibroblast monolayers derived from patients with Turner syndrome, and have evaluated SM-C/IGF-I stimulation of both [3H]thymidine incorporation and cell replication. When compared to fibroblasts from normal adults, newborns, and age-matched children, no significant differences were observed in specific binding of [125I]SM-C/IGF-I to fibroblast monolayers, and displacement curves demonstrated similar receptor affinities for all groups. Similarly, equivalent SM-C/IGF-I stimulation of [3H]thymidine incorporation was seen in both Turner and control fibroblasts. In the absence of serum, SM-C/IGF-I, at a concentration of 10-25 ng/ml, stimulated thymidine incorporation 3.7-11.8-fold in Turner fibroblasts and 1.9-9.8-fold in control cells. In combination with 1.0% human hypopituitary serum (HHS), SM-C/IGF-I stimulated thymidine incorporation 20-70-fold in all cell lines. Cell replication in both TS and control cells was increased 90% by the combination of SM-C/IGF-I + 0.5% HHS, and 140% by SM-C/IGF-I + 0.5% HHS + dexamethasone. We conclude that TS fibroblasts have normal SM-C/IGF-I receptors and sensitivity, and are capable of enhanced DNA synthesis and replication following SM-C/IGF-I stimulation.
D000328:Adult; D000367:Age Factors; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I; D008297:Male; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D013002:Somatomedins / Q000378:metabolism* / Q000494:pharmacology; D014424:Turner Syndrome / Q000378:metabolism*
D007328:Insulin; D010455:Peptides; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone