Martha P M, Reiter E O, Dávila N, Shaw M A, Holcombe J H, Baumann G
Department of Pediatrics, Baystate Medical Center, Springfield, Massachusetts 01199.
J Clin Endocrinol Metab. 1992 Dec;75(6):1470-3. doi: 10.1210/jcem.75.6.1464649.
Obesity is associated with normal or increased growth despite diminished GH secretion compared to lean children. The mechanism by which adequate growth is maintained in the presence of low GH levels is unknown, but is possibly mediated at the GH receptor level. To probe this hypothesis, we examined the relationship between GH responsivity, body mass index (BMI) and plasma GH-binding protein (GH-BP)/receptor level in 43 GH-deficient children during treatment with a fixed dose of GH (0.18 mg/kg.week). Before treatment, BMI [expressed as standard deviation score (SDS) for age (BMI-SDS)] did not correlate with either growth velocity or serum insulin-like growth factor-I (IGF-I). In contrast, after 12 months of GH therapy BMI-SDS correlated directly with plasma IGF-I (P < 10(-5)) and growth velocity (P < 10(-3)). These findings parallel those obtained for GH-BP vs. the response to GH, suggesting that BMI and GH-BP are covariants. The interrelationships among BMI, GH-BP, and response to GH were further probed by multiple regression analysis. Partial correlation coefficients vs. response to GH were consistently stronger for GH-BP than for BMI-SDS, indicating that GH-BP is the dominant factor between these two covariants in determining responsiveness to GH. The data suggest a primary role for GH-BP/receptor levels in determining GH action, with secondary but significant effects of nutrition and degree of adiposity. The latter may be mediated through the impact of nutrition and body mass on GH-BP/receptor levels.
与瘦小孩相比，肥胖儿童尽管生长激素（GH）分泌减少，但仍具有正常生长或生长加速的情况。在生长激素水平较低的情况下仍能维持足够生长的机制尚不清楚，但可能是在生长激素受体水平介导的。为了探究这一假设，我们在43名生长激素缺乏的儿童接受固定剂量生长激素（0.18mg/kg·周）治疗期间，研究了生长激素反应性、体重指数（BMI）与血浆生长激素结合蛋白（GH-BP）/受体水平之间的关系。治疗前，BMI[以年龄标准差评分（SDS）表示（BMI-SDS）]与生长速度或血清胰岛素样生长因子-I（IGF-I）均无相关性。相反，生长激素治疗12个月后，BMI-SDS与血浆IGF-I（P<10-5）和生长速度（P<10-3）直接相关。这些发现与生长激素结合蛋白与生长激素反应的研究结果相似，表明BMI和生长激素结合蛋白是协变量。通过多元回归分析进一步探究了BMI、生长激素结合蛋白和生长激素反应之间的相互关系。与生长激素反应的偏相关系数，生长激素结合蛋白始终比BMI-SDS更强，表明在决定对生长激素的反应性方面，生长激素结合蛋白是这两个协变量中的主导因素。数据表明生长激素结合蛋白/受体水平在决定生长激素作用中起主要作用，营养和肥胖程度有次要但显著的影响。后者可能是通过营养和体重对生长激素结合蛋白/受体水平的影响来介导的。
