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.
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.
Stewart
C E
CE
Department of Molecular & Cellular Physiology, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, UK.
Bates
P C
PC
Calder
T A
TA
Woodall
S M
SM
Pell
J M
JM
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D004392:Dwarfism / Q000503:physiopathology*; D005260:Female; D007106:Immune Sera / Q000276:immunology; D007116:Immunization, Passive; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D051381:Rats; D011922:Rats, Mutant Strains; D011994:Recombinant Proteins / Q000276:immunology; D012756:Sheep / Q000276:immunology; D015430:Weight Gain
D000906:Antibodies; D002352:Carrier Proteins; D007106:Immune Sera; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I