DIFFERENCES IN THE ASSOCIATION OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) AND IGF-I VARIANTS WITH RAT, SHEEP, PIG, HUMAN AND CHICKEN PLASMA-BINDING PROTEINS

Associations between labelled insulin-like growth factors (IGFs) and I GF-binding proteins in plasma have been compared in the rat, sheep, hu man, pig and chicken. The IGFs tested were recombinant human IGF-I, th e truncated variant, des(1-3)IGF-I, and LR(3)IGF-I, an extended form t hat had been engineered so as to minimize interactions with IGF-bindin g proteins. Marked species differences were demonstrated, notably that the IGF-I variants which exhibited extremely weak binding in rat plas ma bound significantly in plasma from the other species. This result w as shown both by size-exclusion chromatography of labelled IGFs added to plasma, in which the extent of variant IGF-I binding decreased in t he order sheep>human>pig=ckicken>rat, and by competition for labelled IGF-I binding in vitro, in which the order was pig=chicken>sheep>human >rat. Notwithstanding these differences, the two IGF-I variants showed only slight between-species binding differences when tested with puri fied rat, sheep and human IGF-binding protein-3. Ligand blotting exper iments with plasma from the fivespecies similarly showed a consistent pattern in that IGF-I binding was much greater than des(1-3)IGF-I bind ing, which in turn was greater than LR(3)IGF-I binding. These experime nts suggest first that IGF-binding properties measured after the remov al of endogenous IGFs do not always reflect the situation with untreat ed plasma secondly, the increased potencies of des(1-3)IGF-I and LR IG F-I in rat growth studies that have been ascribed to higher concentrat ions of these peptides in the free form cannot necessarily be extended to other species.