Insulin-like growth factor I receptors in adult rat liver: characterization and in vivo regulation.
Although the presence of significant amounts of insulin-like growth factor (IGF)-I receptors in fetal tissues is well documented, adult liver has been reported to contain little or no IGF-I binding activity. In the present investigation, substantial amounts of specific IGF-I receptors were detected in crude membrane fractions and in partially purified receptor preparations of female adult rat liver. Insulin was 100 times less potent than IGF-I in competing for 125I-IGF-I binding. IGF-I binding activity was much less than that of insulin binding in both the microsomal fraction and partially purified receptor preparations. Affinity cross-linking of 125I-IGF-I to purified receptors and microsomal fractions followed by electrophoretic analysis under nonreducing conditions revealed labeling of proteins with relative molecular weight (Mr) of 350,000 and 210,000-220,000, corresponding to the molecular mass of the intact tetramer and alpha-beta dimers, respectively. Under reducing conditions, the labeling of proteins with Mr of 130,000 and 260,000, corresponding to the alpha-subunit of IGF-I receptor and its dimer, respectively, was observed. Treatment of microsomes as well as partially purified receptors with 0.5-1 mM dithiothreitol resulted in decreased IGF-I binding, and this correlated with structural changes in the receptor as detected by affinity labeling and electrophoretic analysis. Hepatic IGF-I binding activity was significantly diminished in female rats exposed to chronic growth hormone excess, suggesting down-regulation of IGF-I receptors by the enhanced circulating levels of IGF-I in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Venkatesan
N
N
Department of Medicine, Cedars-Sinai Medical Center, University of California, Los Angeles 90048.
Davidson
M B
MB
D000818:Animals; D002460:Cell Line; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D006706:Homeostasis; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008970:Molecular Weight; D010911:Pituitary Neoplasms / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF; D011972:Receptor, Insulin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*
D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin; D004229:Dithiothreitol