Preferential association of the insulin-like growth factors I and II with metabolically inactive and active carrier-bound complexes in serum.
Ion-exchange chromatography of serum on DEAE-Sephadex A-50 using a stepwise NaCl gradient showed that complexes enriched with insulin-like growth factors I and II (IGF-I and IGF-II) could be preferentially eluted. A fraction eluted with 0.075 M-NaCl preferentially contained immunoreactive IGF-I with peak levels appearing in fractions of Mr approx. 110,000. The IGF-I-binding protein complex itself had low bioactivity as measured in a non-suppressible insulin-like (NSILA) bioassay. On conversion to free IGF-I by gel-permeation chromatography on Sephadex G-75 in 1% formic acid, however, the IGF-I did express its intrinsic NSILA bioactivity. In contrast, an IGF-II-enriched complex was eluted from the DEAE-Sephadex with 0.15 M-NaCl. Practically all of the recovered NSILA of the original serum was present in this fraction, in the Mr range 70,000-300,000 with a peak of 150,000. Chromatography on Sephadex G-75 in 1% formic acid separated this high-Mr NSILA into low-Mr (less than 15000) IGF-II and high-Mr acid-stable NSILA-P. The high-Mr IGF-II complex bound to concanavalin A-Sepharose, suggesting that it was a glycoprotein. The results confirm previous reports that a large portion of the NSILA of whole serum can be accounted for by a biologically active acid-dissociable complex. These data show for the first time that this active complex consists of an IGF-II-preferring binding protein. In direct contrast, the IGF-I-preferring complex does not express NSILA bioactivity until the IGF-I is liberated through acidification. The presence of a metabolically active IGF-II complex in serum raises questions as to its possible biological role in the adult.
D002352:Carrier Proteins / Q000097:blood*; D002846:Chromatography, Affinity; D002852:Chromatography, Ion Exchange; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000097:blood* / Q000276:immunology; D007335:Insulin-Like Growth Factor II / Q000097:blood* / Q000276:immunology; D046911:Macromolecular Substances; D013002:Somatomedins / Q000097:blood* / Q000276:immunology / Q000378:metabolism
D002352:Carrier Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D046911:Macromolecular Substances; D013002:Somatomedins