Insulin-like growth factor-I effect on chicken hepatoma cells (LMH) is inhibited by endogenous IGF-binding proteins.
LMH chicken hepatoma cells show type 1 IGF receptors and a 28 kDa IGF-binding protein (IGFBP) on their membranes. They also secrete large amounts of the 28 kDa IGFBP. Following overnight incubation in serum-free medium, human IGF-I was markedly less effective than insulin in stimulating amino acid (AIB) uptake. Chicken and human IGF-I were equipotent, consistent with their equipotency in inhibiting [125I]IGF-I binding to wheat germ agglutinin-purified IGF receptors or membrane solubilized IGFBP. When cells were supplied with fresh medium, cell-associated IGFBP were unaffected, but the level of soluble IGFBP was largely reduced. This potentiated the effect of IGF-I on AIB uptake. The effect of chicken Long-[Arg3]-IGF-I, which exhibited low affinity for the IGFBP, was unchanged. In fresh or conditioned medium, this analog was more potent than IGF-I, suggesting that both soluble and membrane-bound 28 kDa IGFBP inhibited the effect of IGF-I.
Duclos
M J
MJ
Endocrinologie de la Croissance et du Métabolisme, Station de Recherches Avicoles, Institut National de la Recherche Agronomique, Nouzilly, France.
Chevalier
B
B
Upton
Z
Z
Simon
J
J
D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular; D002462:Cell Membrane / Q000378:metabolism; D002645:Chickens; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D012995:Solubility; D014407:Tumor Cells, Cultured; D014909:Wheat Germ Agglutinins / Q000378:metabolism
D000621:Aminoisobutyric Acids; D017077:Culture Media, Conditioned; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D008565:Membrane Proteins; D014909:Wheat Germ Agglutinins; C085700:long R(3)-insulin-like growth factor-I; C100049:2-aminoisobutyric acid; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1