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)
Identification and characterization of insulin-like growth factor receptors on adult rat cardiac myocytes: linkage to inositol 1,4,5-trisphosphate formation.
