title: Plasma half-lives of native and modified insulin-like growth factor-I in lambs.
abstract: The clearance of labelled insulin-like growth factor-I (IGF-I) has been measured in lambs following acid gel-permeation chromatography and immunoprecipitation of plasma samples. The half-lives obtained in three experiments were between 5 and 7h. Chromatography at neutral pH on a Fractogel HW55(S) column demonstrated that all the radioactivity associated with undegraded peptide in plasma was bound to a carrier protein. Similar studies with IGF-I that had been reduced by prior dithiothreitol treatment showed that two-thirds of the initial radioactivity in plasma decayed with a much shorter half-life and represented material that did not bind to carrier proteins in plasma. The remaining radioactivity was both associated with a binding protein and exhibited the characteristically long half-life of the native growth factor. Analysis of plasma samples using reversed-phase chromatography demonstrated that the radioactive component with a long half-life was IGF-I while that with a short half-life had been reoxidized to an incorrect form of the growth factor. When reoxidation of reduced IGF-I was blocked by S-carboxymethylation before injection of the radioactive peptide into lambs, it remained unbound in plasma and had a 0.8-0.9 h half-life. We suggest that reduced IGF-I only associates with the binding protein upon oxidation and correct folding and that this association is necessary in order for IGF-I to have a relatively long half-life.
authors: CSIRO Division of Human Nutrition, Adelaide, Australia.
authors: G L
authors: GL
authors: Francis
authors: P J
authors: PJ
authors: McNamara
authors: O H
authors: OH
authors: Filsell
authors: F J
authors: FJ
authors: Ballard
mesh_terms: D000818:Animals; D006207:Half-Life; D007334:Insulin-Like Growth Factor I / Q000097:blood* / Q000493:pharmacokinetics; D012756:Sheep; D013002:Somatomedins / Q000097:blood*
chemical_list: D013002:Somatomedins; D007334:Insulin-Like Growth Factor I