Evidence supporting a direct suppressive effect of growth hormone on serumIGFBP-1 levels. Experimental studies in normal, obese and GH-deficient adults

It has occasionally been suggested that GH directly suppresses circulating IGFBP-1 levels, although it is generally believed that such an effect is se condary to a GH-induced increase in insulin levels. We present data from se veral experiments in which the effects of GH on IGFBP-1 could be studied mo re extensively. In normal subjects (n=36), an i.v. GH bolus caused a small but significant decrease in plasma IGFBP-1 concentrations without changes i n insulin [IGFBP-1 (mu g/l): 2.6 +/- 0.3 (GH) vs 3.2 +/- 0.4 (placebo), P<0 .05]. Conversely, a 28-h somatostatin infusion with and without GH administ ration during fasting in normal subjects yielded higher IGFBP-1 levels in t he non-GH substituted study [50.5 +/- 5.3 (GH-suppression) vs 22.6 +/- 5.6 (GH-substitution), P<0.01], comparable with an increased concentration of I GFBP-1 during fasting in GH-deficient patients without usual GH substitutio n [23.4 +/- 7.6 (GH pause) vs 14.1 +/- 4.9 (GH substitution), P<0.01]. in b oth fasting studies insulin levels remained stable, During a hypocaloric di et, long-term GH treatment in obesity lead to a significant decline in IGFB P-1 level (2.3 +/- 0.6 vs 1.2 +/- 0.2, P<0.01), while no changes were found in the placebo group. Again, insulin levels remained equally low in both s tudies. Finally, a significant rebound increase in IGFBP-1 level in respons e to insulin induced hypoglycemia was only observed among GH-deficient pati ents, but not in control subjects, the latter of whom responded to hypoglyc emia with a significant increase in serum GH levels [23.2 +/- 7.2 (GHDA) vs 2.5 +/- 0.3 (controls), P<0.01]. In conclusion, a suppressive effect of GH on IGFBP-1 appears to be unmasked in the presence of low or suppressed ins ulin levels, making GH a potential regulator of IGF-I bioactivity in a hith erto unrecognized way. (C) 1999 Churchill Livingstone.