Potentiation of insulin-like growth factor-I (IGF-I) activity by an antibody: supportive evidence for enhancement of IGF-I bioavailability in vivo by IGF binding proteins

• Published in: Endocrinology (Philadelphia) Vol. 133; no. 3; p. 1462
• Main Authors: Stewart, C E, Bates, P C, Calder, T A, Woodall, S M, Pell, J M
• Format: Journal Article
• Language: English
• Published: United States 01.09.1993
• Subjects: Animals; Antibodies - metabolism; Carrier Proteins - physiology; Dwarfism - physiopathology; Female; Immune Sera - immunology; Immunization, Passive; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I - immunology; Insulin-Like Growth Factor I - pharmacology; Insulin-Like Growth Factor I - physiology; Male; Mice; Mice, Mutant Strains; Rats; Rats, Mutant Strains; Recombinant Proteins - immunology; Sheep - immunology; Weight Gain
• ISSN: 0013-7227
• DOI: 10.1210/endo.133.3.7689959

The effects of ovine polyclonal antibodies raised against human recombinant IGF-I were investigated in GH-deficient rodents in vivo both in the presence and absence of exogenous IGF-I. Dwarf mice (negligible endogenous serum IGF-I) treated with anti-IGF-I serum which had been pre-incubated with IGF-I exhibited a significantly greater rate of daily weight gain than did mice treated with the same dose of IGF-I alone (P < 0.001) or even a 2.5-fold higher dose (P < 0.001). Similar increases in whole body weight gain were observed in dwarf rats, with a concomitant increase in dissected muscle weight. Serum IGF-I concentrations were greater in all animals treated with the complex of anti-IGF-I antibodies and IGF-I than in those administered only IGF-I. Size exclusion chromatography of dwarf rat serum indicated the presence of high mol wt material (> 160 kDa) capable of binding 125I-IGF-I in the anti-IGF-I treated rats. We suggest that this particular polyclonal antibody is behaving in a similar manner to an enhancing IGF binding protein, maintaining a reservoir of bioactive IGF-I. Since the antibody has a slightly lower affinity (2 x 10(8) liters/M) than that of the type 1 receptor, these data provide tentative indirect evidence to support the hypothesis that the recently discovered mechanisms which apparently decrease the affinities of several IGFBPs may indeed result in increased IGF-I bioavailability.