SERUM CONCENTRATIONS OF INSULIN-LIKE GROWTH-FACTORS (IGFS), IGF BINDING-PROTEIN-1 AND BINDING-PROTEIN-3 AND GROWTH-HORMONE BINDING-PROTEIN IN OBESE WOMEN AND THE EFFECTS OF GROWTH-HORMONE ADMINISTRATION - A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

Obesity is associated with suppressed growth hormone (GH) concentrations but relatively little is known about insulin-like growth factors(IGFs) and binding proteins for GH and IGFs (GHBP and IGFBPs) and the modulatory effect of GH administration. In a double-blind, crossover design we studied the impact of 5 weeks of placebo or GB administration (0.03 mg . kg(-1) body wt . day(-1)) in nine obese women (mean +/- SEM: age 30.4 +/- 2.4 years; body mass index 37.0 +/- 2.8 kg/m(2)) on IGF-I, IGF-II, IGFBP-1 and -3 and GHBP. Serum IGF-I (mu g/l) levels were subnormal and increased significantly following GH (117 +/- 16 (placebo) vs 434 +/- 33 (GH) vs 198 +/- 15 (control (p < 0.01)). By contrast, serum IGF-II (mu g/l) levels were in the normal range and remained unchanged (608 +/- 20 (placebo) vs 647 +/- 40 (GH) (NS)). Serum IGFBP-3 was in the normal range and increased significantly during GH treatment, although relatively less than IGF-I, such that the molar ratio between IGF-I and TGFBP-3 increased with GH treatment, whereas the ratio between IGF-I + IGF-II and IGFBP-3 remained unchanged, Serum IGFBP-1 was low in the placebo situation but became further and almost completely suppressed during GH treatment. During a 2-h hyperinsulinemic, euglycemic glucose clamp, IGFBP-1 decreased in the placebo study and remained suppressed during GH, Serum GHBP (nmol/l) levels were elevated substantially compared to non-obese controls (p < 0.001) and did not change during GH treatment (2.37 +/- 0.36 (placebo) vs 2.21 +/- 0.25 (GH) vs 0.80 +/- 0.19 (control)), In conclusion, obese subjects have low total IGF-I levels but may exhibit relatively increased free IGP-I levels due to the suppression of IGFBP-1. This presumed elevation in free IGF-1 in obesity may explain the normal levels of IGFBP-3 and IGF-II, which contrasts with classic GH deficiency. Furthermore, obese subjects are responsive to exogenous GH in terms of total IGF-I generation and normalization of the ratio between IGF-I and IGFBP-3, Finally, obesity is associated with marked elevations in GHBP levels that were unaffected by 5 weeks of GH administration.