Insulin-like growth factor binding proteins from cultured human fibroblasts. Characterization and hormonal regulation.
Specific, high affinity insulin-like growth factor (IGF) binding proteins are secreted by human fibroblasts in culture. By multiple criteria, the species of IGF binding proteins produced by human fibroblasts are distinct from the HepG2/amniotic fluid IGF binding protein, but share many characteristics with the growth hormone-dependent IGF binding protein forms predominant in normal adult human plasma. Treatment of cultured human fibroblasts with growth hormone produced an increase in IGF binding protein activity in the medium, while addition of glucocorticoids markedly diminished IGF binding activity. Insulin, epidermal growth factor, platelet-derived growth factor, and progesterone had no effect on IGF binding activity in fibroblast media. In comparison, HepG2 IGF binding activity was enhanced by progesterone, decreased by insulin, and unaffected by growth hormone or glucocorticoid treatment. Five molecular forms of IGF binding proteins were identified by Western ligand blots in human fibroblast conditioned medium, with Mr = 41,500, 37,000, 32,000, 28,000, and 23,000. In human fibroblast conditioned medium, the Mr = 41,500 and 37,000 IGF binding protein species were abundant, as in normal human plasma, with a major Mr = 23,000 form which was a minor component in plasma.
Conover
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Department of Pediatrics, Stanford University, California 94305.
Liu
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Powell
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Rosenfeld
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Hintz
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D000818:Animals; D001667:Binding, Competitive; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007700:Kinetics; D008113:Liver Neoplasms / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D011374:Progesterone / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology; D012313:RNA / Q000032:analysis; D051381:Rats; D012756:Sheep; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D011479:Protamines; D011374:Progesterone; D012313:RNA; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D013006:Growth Hormone; D006854:Hydrocortisone