The Growth Hormone (GH) - Binding Protein in Obesity with Varying Glucose Tolerance: Relationship to Body fat Distribution Sex Hormones, Insulin and GH-Insulin-Like Growth Factor (IGF)-1 Axis / 대한내분비학회지

ABSTRACT

BACKGROUND: As GHBP is believed to be derived from proteolytic cleavage of the extracellular domain of the GH receptor and may be regarded as an intrinsic part of the GH-IGF-1 axis, an effect of body composition on circulating GHBP levels may be expected. We investigated GHBP variations in obesity with varying glucose tolerance and its relationship to body fat distribution, sex hormones, insulin secretion, and the GH-IGF-1 axis. METHODS: Bioelectrical impedence for measurement of total body fat and computed tomography for visceral fat and subcutaneous fat at umbilicus level were performed in 69 obese Koreans and 21 lean Koreans. Insulin secretion in response to an oral glucose tolerance test (OGTT) and a GH stimulation test by L-dopa, growth hormone-binding protein (GHBP), insulin-like growth factor (IGF)-1 and sex hormones (estrone, estradiol, total and free testosterone) were measured. RESULTS: Obese type 2 DM group had the highest GHBP levels and the most visceral fat amount. GHBP levels were most strongly correlated with the ratio of visceral fat area to body weight (VWR) above other parameters (r=0.725, p<0.001). Insulin- and free fatty acid-area under the curve (AUC) during OGTT and IGF-1 level were also positively correlated with GHBP levels (r=0.474, p<0.005; r=0.572, p<0.005; r=0.453, p<0.005). GH-AUC to L-dopa stimulation test was negatively correlated with GHBP levels (r=0.432, p<0.005). The GHBP level was slightly higher in females than in male in the same glucose tolerance category. In males, total and free testosterone levels were negatively correlated with GHBP levels (r=-0.516, p<0.001;r=-0.653, p<0.001). Stepwise multiple linear regression analysis showed that VWR, FFA-and insulin-AUC significantly contributed to the variability of GHBP (r=0.58). CONCLUSION: We demonstrated that 1) visceral fat amount was mainly determined GHBP levels in obese subjects with varying glucose tolerance; 2) hyperglycemia per se did not influence GHBP level, whereas insulin and FFA could play a role in regulation of GHBP level. 3) The constant concentration of IGF-1 despite GH hyposecretion suggests that increased GHBP level retlect GHBP hypersensitivity in order to compensate for decreased GH secretion in obesity; 5) the lower level of GHBP in males might be explained at least in part by a suppressive effect of androgen.