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):1464-9. doi: 10.1210/jcem.75.6.1464648.
Individual growth rates (or responses to GH therapy) and adult heights vary over a wide range. The reasons for this variation are poorly understood. Based on the reciprocal relationship between GH production and serum GH-binding protein/receptor (GH-BP), we hypothesized that genetic growth potential was achieved by a specific combination of GH-BP/receptor and GH production in each individual. To address the question whether GH production regulates GH-BP, or vice versa, we studied GH-deficient children, where one of the parameters, GH exposure, could be controlled through exogenous administration. Forty-three untreated prepubertal GH-deficient children were studied before and after 6 and 12 months of GH replacement therapy (0.18 mg/kg.week). Growth velocity, height, bone age, weight and their respective Z scores, serum GH-BP, and serum insulin-like growth factor I (IGF-I) were measured at each time point. The patients responded with significant increases in serum IGF-I, age-adjusted growth velocity, and height (P < 10(-6) for all). Before therapy, GH-BP correlated directly with chronologic and bone age (P < 10(-4), but not with either growth velocity or IGF-I. In contrast, GH-BP correlated strongly with the response to therapy whether assessed as the incremental change in IGF-I (P < 10(-6)) or as the increase in growth velocity (P approximately 0.003). GH treatment had no consistent effect on GH-BP/receptor levels. These findings support the concept that the GH-BP/receptor endowment is characteristic for an individual and plays a pivotal role in somatic growth. The GH-BP/receptor system and its ontogeny appears relatively independent of regulation by GH. Differences in individual GH-BP/GH receptor complement account for some of the variability in the response to GH, and GH-BP levels may serve as a predictor for the degree of response. The reciprocal relationship between GH production and GH-BP in normal subjects probably results from adjustment of GH secretion to accommodate the prevailing GH-BP/receptor environment.
个体生长速率（或对生长激素治疗的反应）以及成人身高差异很大。造成这种差异的原因尚不清楚。基于生长激素分泌与血清生长激素结合蛋白/受体（GH-BP）之间的相互关系，我们推测，个体的遗传生长潜力是由GH-BP/受体与生长激素分泌的特定组合实现的。为了探究是生长激素分泌调节GH-BP，还是相反，我们研究了生长激素缺乏的儿童，在这些儿童中，通过外源性给药可以控制其中一个参数，即生长激素暴露。对43名未经治疗的青春期前生长激素缺乏儿童在接受生长激素替代治疗（0.18mg/kg·周）6个月和12个月前后进行了研究。在每个时间点测量生长速度、身高、骨龄、体重及其各自的Z评分、血清GH-BP和血清胰岛素样生长因子I（IGF-I）。患者血清IGF-I、年龄校正生长速度和身高显著增加（均P<10^(-6)）。治疗前，GH-BP与实际年龄和骨龄直接相关（P<10^(-4)），但与生长速度或IGF-I均无相关性。相比之下，无论以IGF-I的增量变化（P<10^(-6)）还是生长速度的增加（P约为0.003）来评估，GH-BP与治疗反应均密切相关。生长激素治疗对GH-BP/受体水平没有一致的影响。这些发现支持了这样的概念，即GH-BP/受体禀赋是个体特有的，并且在身体生长中起关键作用。GH-BP/受体系统及其个体发生似乎相对独立于生长激素的调节。个体GH-BP/生长激素受体互补性的差异是对生长激素反应变异性的部分原因，并且GH-BP水平可能作为反应程度的预测指标。正常受试者中生长激素分泌与GH-BP之间的相互关系可能是由于生长激素分泌的调整以适应主要的GH-BP/受体环境。
