POTENTIATION OF INSULIN-LIKE GROWTH FACTOR-I (IGF-I) ACTIVITY BY AN ANTIBODY - SUPPORTIVE EVIDENCE FOR ENHANCEMENT OF IGF-I BIOAVAILABILITYIN-VIVO BY IGF BINDING-PROTEINS

The effects of ovine polyclonal antibodies raised against human recomb inant IGF-I were investigated in GH-deficient rodents in vivo both in the presence and absence of exogenous IGF-I. Dwarf mice (negligible en dogenous 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 concomitan t increase in dissected muscle weight. Serum IGF-I concentrations were greater in all animals treated with the complex of anti-IGF-I antibod ies and IGF-I than in those administered only IGF-I. Size exclusion ch romatography of dwarf rat serum indicated the presence of high mol wt material (>160 kDa) capable of binding I-125-IGF-I in the anti-IGF-I t reated rats. We suggest that this particular polyclonal antibody is be having in a similar manner to an enhancing IGF binding protein, mainta ining a reservoir of bioactive IGF-I. Since the antibody has a slightl y lower affinity (2 x 10(8) liters/M) than that of the type 1 receptor , these data provide tentative indirect evidence to support the hypoth esis that the recently discovered mechanisms which apparently decrease the affinities of several IGFBPs may indeed result in increased IGF-I bioavailability.