The distal axis of growth hormone (GH) in nutritional disorders: GH-binding protein, insulin-like growth factor-I (IGF-I), and IGF-I receptors in obesity and anorexia nervosa

Abstract

The endocrine abnormalities along the growth hormone (GH) axis in anorexia nervosa (AN) and in obesity include hypothalamic, pituitary, and peripheral elements. The present study was undertaken to evaluate the effects of these nutritional extremes on GH-binding protein (BP) levels and on insulin-like growth factor-I (IGF-I) receptors on red blood cells (RBC). Nine patients with AN and 20 obese subjects were compared with normal control children, adolescents, and adults. GH-BP was measured by a binding assay with dextran-coated charcoal separation. IGF-I binding was measured on enriched RBC. Serum GH-BP levels were markedly reduced in the AN patients, and highly increased in the obese. Scatchard analyses showed linear plots with unaltered binding affinities (Ka). The binding capacity (Bmax) was significantly lower than normal control in the AN patients and higher in the obese. GH-BP levels correlated positively with the body mass index (BMI). RBC [ 125I]IGF-I binding was significantly elevated in the AN patients and low in the obese. Scatchard analyses showed curvilinear plots. The high-affinity constants (Ka 1) were slightly, but significantly, higher in the AN patients and in the obese compared with control. The binding capacity of the first binder (Bmax 1) was lower in obesity than in AN or control. The low-affinity constants (Ka 2) were similar in the three groups, and its binding capacity (Bmax 2) was similar in the AN patients and the controls, but significantly lower in the obese. [ 125I]IGF-I binding correlated negatively and significantly with the BMI and with the GH-BP. AN, with low GH-BP and high IGF-I receptors, can, therefore, be viewed as a condition of GH resistance and IGF-I hypersensitivity. On the other hand, obesity, with high GH-BP and low IGF-I receptors, can be viewed as a condition with GH hypersensitivity and IGF-I resistance. Taken together, these results indicate positive correlation between BMI and GH responsiveness, and negative correlation between BMI and IGF-I responsiveness. The results of the present study show that these two phenomena correlate negatively with each other.