DIFFERENTIAL LONG-TERM EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I), GROWTH-HORMONE (GH), AND IGF-I PLUS GH ON BODY GROWTH AND IGF BINDING-PROTEINS IN HYPOPHYSECTOMIZED RATS

The long-term effects of recombinant human insulin-like growth factor- I (rhIGF-I) and GH (rhGH) on body growth and the IGF-I/IGF binding pro tein (IGFBP)/acid-labile subunit (ALS) axis were investigated in hypop hysectomized (hypox) rats given excipient, rhIGF-I (2 mg/kg day sc, mi nipumps), rhGH (2 mg/kg day, sc, daily injections), or rhIGF-I plus rh GH for 28 days. The relative growth-promoting activity of the treatmen ts was rhGH plus rhIGF-I more than rhGH more than rhIGF-I. Weight gain induced by rhIGF-I progressively declined after 4 days, compared with a more maintained effect of rhGH. At day 28, growth responses did not correlate with serum IGF-I levels [rhGH plus rhIGF-I (492 +/- 140) > rhIGF-I (322 +/- 75) > rhGH (85 +/- 26) > control (39 +/- 7 ng/ml)]. S erum ALS concentrations in hyper rats were remarkably low (0.42 +/- 0. 04 mu g/ml) but were restored toward normal by rhGH (12.55 +/- 4.78) o r rhGH plus rhIGF-I (12.85 +/- 6.64) but not by rhIGF-I alone (0.85 +/ - 0.25). Antibodies against rhGH were present at day 28, with titer be ing negatively related to weight gain, IGF-I, and ALS levels. All trea tments increased serum IGFBP-3. The molecular size distribution of IGF BP-3 in rhGH-treated rats was similar to that of normal rats (IGFBP-3 in the 150K mol wt range), due to rhGH increasing serum ALS, but was a ltered by rhIGF-I (IGFBP-3 in the 200-300K and 44K mol wt range). In a GH-deficient animal, restoring the IGF/1GFBP-3/ALS axis towards norma l is associated with greater growth promotion.