PASSIVE-IMMUNIZATION AGAINST INSULIN-LIKE GROWTH FACTOR-I DOES NOT INHIBIT GROWTH HORMONE-STIMULATED GROWTH OF DWARF RATS

Passive immunization against insulin-like growth factor-I (IGF-I) was undertaken in GH-deficient rats in an attempt to elucidate the relative importance of the endocrine vs. autocrine/paracrine actions of IGF-I in stimulating growth. Antiserum against IGF-I was raised in sheep and purified by affinity chromatography. The ability of the purified antibodies to neutralize the actions of IGF-I in vitro and bind IGF-I in vivo were extensively tested using L6 myoblast and cartilage bioassays. Four groups of male rats with isolated GH deficiency were used in the study. At 49 days of age the rats received 100-mu-l normal saline given sc each day for 10 days, 2 mg/kg recombinant bovine GH (bGH) given in 100-mu-l, sc, each day, 2 mg/kg bGH, sc, and 300-mu-l immunoglobulin G purfied from normal sheep serum given daily ip, or 2 mg/kg bGH plus 300-mu-l anti-IGF-I immunoglobulin G daily, ip (a dose that was able to completely inhibit IGF-I actions on sulfate uptake into cartilage). Treatment with GH significantly increased growth rates (P < 0.001) in the rats, but there was no difference between any of the three GH-treated groups; passive immunization against IGF-I did not diminish the GH-stimulated growth in these rats. Excess antibody could be detected in the plasma of all anti-IGF-I-treated rats at the conclusion of the experiment, and the antibody was capable of sequestering both free and binding protein-bound IGF-I. The absence of even a slight retardation of GH-stimulated growth in the anti-IGF-I-treated rats suggests that circulating IGF-I may not be important in mediating the growth-promoting actions of GH, although the immunoneutralization probably does not affect GH stimulation of tissue IGF-I production.