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

Year: 2018
Type: article
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 < 0.0001) and bioactive IGF (1.29 ± 0.39 to 2.60 ± 1.12 μg/L, p < 0.0001). The treatment-related increase in bioactive IGF, but not total IGF-I concentration, predicted an increase in lean mass (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.
DOI: 10.1016/j.ghir.2018.03.003
Authors: Laura E. Dichtel, Mette Bjerre, Melanie Schorr, Miriam A. Bredella, Anu V. Gerweck, Brian M. Russell, Jan Frystyk, Karen K. Miller
Language: English
Field: Medicine
Open Access status: bronze
Funders: Harvard University, Harvard Catalyst, Aarhus Universitet, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: The Growth Hormone and Insulin-like Growth Factor-1 Axis in Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis, Bone Metabolism in Adolescents UndergoingBariatric Surgery, G2496518617, Harvard Clinical and Translational Science Center (UL1), Growth Hormone and Cardiovascular Disease, EFFECTS OF GROWTH HORMONE ON INTRAMYOCELLULAR LIPIDS, GH, Cardiovascular Risk and Visceral Adiposity in Women, Harvard Clinical and Translational Science Center, Training Program in Endocrinology
OpenAlex ID: W2793560270
FWCI: 1.193
Cites: 51
Cited by: 12
Related to: 10