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

• Published in: Endocrinology (Philadelphia) Vol. 137; no. 5; pp. 1913 - 1920
• Main Authors: Fielder, P J, Mortensen, D L, Mallet, P, Carlsson, B, Baxter, R C, Clark, R G
• Format: Journal Article
• Language: English
• Published: Washington Oxford University Press 01-05-1996
• Subjects: Growth factors; Growth hormones; Insulin; Insulin-like growth factor I; Insulin-like growth factor-binding protein 3; Insulin-like growth factors; Long-term effects; Proteins; Size distribution; Weight
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.137.5.8612531

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 protein (IGFBP)/acid-labile subunit (ALS) axis were investigated in hypophysectomized (hypox) rats given excipient, rhIGF-I (2 mg/kg.day s.c., minipumps), rhGH (2 mg/kg.day, s.c., daily injections), or rhIGF-I plus rhGH for 28 days. The relative growth-promoting activity of the treatments 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)]. Serum ALS concentrations in hypox rats were remarkably low (0.42 +/- 0.04 micrograms/ml) but were restored toward normal by rhGH (12.55 +/- 4.78) or 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 being negatively related to weight gain, IGF-I, and ALS levels. All treatments increased serum IGFBP-3. The molecular size distribution of IGFBP-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 altered by rhIGF-I (IGFBP-3 in the 200-300K and 44K mol wt range). In a GH-deficient animal, restoring the IGF/IGFBP-3/ALS axis towards normal is associated with greater growth promotion.