Insulin-like growth factor I (IGF-I)-binding protein complex is a better mitogen than free IGF-I.
The insulin-like growth factors (IGF)-I and -II are bound to specific carrier proteins in the circulation. For investigation of their physiological role, the acid-stable subunit of the major binding protein (SmBP) was isolated from human plasma Cohn fraction IV. Its effect on the mitogenic activity of IGF-I was studied with baby hamster kidney fibroblasts (BHK-21) and human skin fibroblasts. While free IGF-I had no effect on thymidine incorporation into DNA with BHK-21 cells and only a moderate effect with human fibroblasts under standard conditions, DNA synthesis was significantly enhanced with both cell lines if IGF-I was complexed with SmBP before the experiment. The enhancement was optimal at an approximately equimolar ratio of both peptides. In contrast to experiments in which large concentrations of IGF-I were added at the beginning, repeated addition of small quantities of free IGF-I at hourly intervals clearly stimulated DNA synthesis in BHK-21 cells. Binding studies with radiolabeled SmBP revealed no evidence for direct interaction with either cell line. It is concluded that SmBP acts as a reservoir, releasing continuously low amounts of IGF-I and thereby creating a steady state situation of receptor occupancy, which appears to be a better mitogenic stimulus than temporary large concentrations of IGF-I.
Blum
W F
WF
University Children's Hospital, Tübingen, West Germany.
Jenne
E W
EW
Reppin
F
F
Kietzmann
K
K
Ranke
M B
MB
Bierich
J R
JR
D001798:Blood Proteins / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D007668:Kidney / Q000166:cytology; D008934:Mitogens / Q000494:pharmacology / Q000502:physiology*; D012867:Skin / Q000166:cytology; D013002:Somatomedins / Q000502:physiology*
D001798:Blood Proteins; D002352:Carrier Proteins; C032309:Cohn fraction IV; D018969:Insulin-Like Growth Factor Binding Proteins; D008934:Mitogens; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I