Veldhuis J D, Iranmanesh A, Ho K K, Waters M J, Johnson M L, Lizarralde G
Division of Endocrinology and Metabolism, University of Virginia, Charlottesville 22908.
J Clin Endocrinol Metab. 1991 Jan;72(1):51-9. doi: 10.1210/jcem-72-1-51.
We have examined the mechanisms underlying reduced circulating GH concentrations in the obese human. Computer-assisted (deconvolution) analysis was used to determine endogenous GH secretory and clearance rates quantitatively from entire 24-h plasma GH concentration profiles. These analyses revealed that the half-life (t 1/2) of endogenous GH was significantly shorter in obese (11.7 +/- 1.6 min) than in normal weight subjects (15.5 +/- 0.81 min; P less than 0.01). The accelerated blood disposal rate of GH was not due to decreased circulating concentrations of GH-binding protein, since the latter were similar in obese (25 +/- 1.0%) and normal weight (24 +/- 2.3%) men. However, obese men had significantly fewer GH secretory bursts (3.2 +/- 0.53 vs. 9.7 +/- 0.67/day; P less than 0.01). Among the rare GH secretory bursts that occurred in obese subjects, there were significantly prolonged mean intersecretory burst intervals (282 +/- 65 vs. 131 +/- 11 min; P less than 0.05). The resultant daily GH production rate in obese men was reduced to one fourth that in normal weight individuals. Both GH secretion rate and burst frequency were negatively correlated with the degree of obesity (ponderal index). The decreases in GH burst frequency and half-life were specific, since GH secretory pulse amplitude (maximal rate of GH release), the mass of GH released per burst, and the duration of computer-resolved GH secretory bursts were not different in obese and normal weight men. We conclude that obese men harbor a double defect in GH dynamics involving both GH secretion and clearance, and that the severity of the GH secretory deficiency is proportionate to the degree of obesity.
我们研究了肥胖人群循环中生长激素（GH）浓度降低的潜在机制。采用计算机辅助（去卷积）分析，根据24小时血浆GH浓度曲线定量测定内源性GH分泌率和清除率。这些分析显示，肥胖者内源性GH的半衰期（t1/2）显著短于正常体重者（分别为11.7±1.6分钟和15.5±0.81分钟；P<0.01）。GH血液清除率加快并非由于GH结合蛋白循环浓度降低，因为肥胖男性（25±1.0%）和正常体重男性（24±2.3%）的GH结合蛋白浓度相似。然而，肥胖男性的GH分泌脉冲显著减少（分别为3.2±0.53次/天和9.7±0.67次/天；P<0.01）。在肥胖受试者中罕见的GH分泌脉冲中，平均脉冲间期显著延长（分别为282±65分钟和131±11分钟；P<0.05）。肥胖男性的每日GH产生率降至正常体重个体的四分之一。GH分泌率和脉冲频率均与肥胖程度（体重指数）呈负相关。GH脉冲频率和半衰期的降低具有特异性，因为肥胖男性和正常体重男性的GH分泌脉冲幅度（GH释放最大速率）、每次脉冲释放的GH量以及计算机解析的GH分泌脉冲持续时间并无差异。我们得出结论，肥胖男性在GH动态变化方面存在双重缺陷，涉及GH分泌和清除，且GH分泌不足的严重程度与肥胖程度成正比。
