The effect of growth hormone on bioactive IGF in overweight/obese women

Abstract Objective Overweight/obesity is characterized by decreased growth hormone (GH) secretion whereas circulating IGF-I levels are less severely reduced. Yet, the activity of the circulating IGF-system appears to be normal in overweight/obese subjects, as estimated by the ability of serum to activate the IGF-I receptor in vitro (bioactive IGF). We hypothesized that preservation of bioactive IGF in overweight/obese women is regulated by an insulin-mediated suppression of IGF-binding protein-1 (IGFBP-1) and IGFBP-2, and by suppression of IGFBP-3, mediated by low GH. We additionally hypothesized that increases in bioactive IGF would drive changes in body composition with low-dose GH administration. Design Cross-sectional analysis and 3-month interim analysis of a 6-month randomized, placebo-controlled study of GH administration in 50 overweight/obese women without diabetes mellitus. Bioactive IGF (kinase receptor activation assay) and body composition (DXA) were measured. Results Prior to treatment, IGFBP-3 ( r  = −0.33, p  = 0.02), but neither IGFBP-1 nor IGFBP-2, associated inversely with bioactive IGF. In multivariate analysis, lower IGFBP-3 correlated with lower peak stimulated GH ( r  = 0.45, p  = 0.05) and higher insulin sensitivity ( r  = −0.74, p  = 0.003). GH administration resulted in an increase in mean serum IGF-I concentrations (144 ± 56 to 269 ± 66 μg/L, p p r  = 0.31, p  = 0.03) and decrease in total adipose tissue/BMI ( r  = −0.43, p  = 0.003). Conclusions Our data suggest that in overweight/obesity, insulin sensitivity and GH have opposing effects on IGF bioactivity through effects on IGFBP-3. Furthermore, increases in bioactive IGF, rather than IGF-I concentration, predicted GH administration-related body composition changes. Clinical Trial Registration Number: NCT00131378 .