CHANGES IN INSULIN-LIKE GROWTH-FACTOR-I (IGF-I), IGF-BINDING PROTEIN-3, GROWTH-HORMONE (GH)-BINDING PROTEIN, ERYTHROCYTE IGF-I RECEPTORS, AND GROWTH-RATE DURING GH TREATMENT

To assess the relative determinants of growth rate, we measured serum levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), and GH-binding protein (GHBP) as well as IGF-I erythrocyte receptor specific binding (SB) in 14 prepubertal GH-deficient children before and during the first year of treatment with 0.043 mg/kg.day GH . Serum IGF-I and IGFBP-3 levels, measured by RIA, were significantly increased by 2 weeks and showed progressive increases throughout the y ear of GH therapy. Growth rate (height velocity so score adjusted for bone age) correlated best with the 12 month changes in IGFBP-3 (r = 0. 81; P < 0.001) and IGF-I (r = 0.72; P = 0.005), and to a lesser extent with the 12 month absolute IGFBP-3 (r = 0.58; P = 0.04) and the 6 mon th change in IGFBP-3 (r = 0.55; P = 0.05). The baseline IGF-I correlat ed inversely with the growth rate during GH therapy (r = -0.55; P = 0. 05) and was the best pretreatment predictor of growth response. GHBP, as measured by Ligand-mediated immunofunctional assay, showed no signi ficant change during GH therapy and did not correlate with growth resp onse. The baseline GHBP, however, did correlate with both the 12 month IGFBP-3 (R = 0.72; P = 0.006) as well as the 2 week change in IGFBP-3 (r = 0.63; P = 0.05). Erythrocyte IGF-I SB showed a significant decre ase by 6 months secondary to a decrease in IGF-I receptor number, with no change in affinity. The 6 month IGF-I receptor binding correlated inversely with the increase in IGF-I (r = -0.88; P < 0.001). Erythrocy te IGF-I SB at baseline did not correlate with the growth response, al though there was an inverse trend between the 6 month IGF-I receptor l evel and the growth rate. IGF-I and IGFBP-3 show progressive increases , whereas the erythrocyte IGF-I receptor-binding capacity decreases by 6 months, and GHBP shows little change during the first year of GH tr eatment. Data from this study suggest that changes in IGFBP-3 and, to a lesser extent, IGF-I are the major correlates of growth rate, and th at down-regulation of the IGF-I receptor may have relatively little in fluence on growth rate compared with changes in IGFBP-3 and IGF-I.