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

• Published in: Growth hormone & IGF research Vol. 40; pp. 20 - 27
• Main Authors: Dichtel, Laura E., Bjerre, Mette, Schorr, Melanie, Bredella, Miriam A., Gerweck, Anu V., Russell, Brian M., Frystyk, Jan, Miller, Karen K.
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01-06-2018
• Subjects: Adult; Bioactive IGF; Biomarkers - blood; Cross-Sectional Studies; Female; Follow-Up Studies; Growth hormone; Human Growth Hormone - administration & dosage; Humans; IGF-I; Insulin-Like Growth Factor Binding Protein 2 - blood; Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-Like Growth Factor I - analysis; Male; Obesity; Obesity - blood; Obesity - drug therapy; Overweight - blood; Overweight - drug therapy; Prognosis; Obesity; IGF-I; Growth hormone; Bioactive IGF
• ISSN: 1096-6374; 1532-2238
• DOI: 10.1016/j.ghir.2018.03.003

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.
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.
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).
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.
•In obesity, insulin sensitivity and GH have opposing effects on IGF bioactivity, as measured by IGF-1R activation.•These effects on IGF-1R activation appear to be mediated through IGFBP-3.•Increase in IGF-1R activation predicted body composition change with GH administration.•In contrast, total IGF-I was not predictive of any body-composition changes.