Boguszewski C L, Jansson C, Boguszewski M C, Rosberg S, Wikland K A, Carlsson B, Carlsson L M
Department of Internal Medicine, Sahlgrenska Hospital, University of Göteborg, Sweden.
Eur J Endocrinol. 1997 Sep;137(3):246-53. doi: 10.1530/eje.0.1370246.
The proportion of non-22 kDa GH isoforms was evaluated in 93 healthy children (48 boys aged 6.8-18.4 years and 45 girls aged 3.9-18.4 years) of normal stature (height +/- 2 s.d. score) at different stages of puberty. In addition, correlations among the proportion of non-22 kDa GH isoforms, auxology, spontaneous GH secretion and biochemical measurements were investigated. Serum non-22 kDa GH levels, expressed as percentage of total GH concentration in the samples, were determined by the 22 kDa GH exclusion assay, in which monomeric and dimeric 22 kDa GH are removed from serum and the non-22 kDa GH isoforms are quantitated using a polyclonal antibody GH assay. Samples were selected from spontaneous GH peaks in 24-h GH profiles. For boys, the median proportion of non-22 kDa GH isoforms was 8.5% (range 3.2-26.6%) and for girls it was 9.6% (1.8-17.4%), with no influence of age and no sex-related difference in prepubertal (boys, 7.2%; girls, 8.8%) or pubertal children (boys, 9.1%; girls, 9.9%). However, the median proportion of non-22 kDa GH isoforms was significantly higher in pubertal boys (9.1%) than in prepubertal boys (7.2%; P = 0.03). In pubertal boys, height S.D. scores (SDS) were inversely correlated to the proportion of non-22 kDa GH isoforms (r = -0.38; P = 0.02), especially at mid-puberty (r = -0.7; P = 0.01), indicating that the presence of increased amounts of circulating non-22 kDa GH isoforms was associated with less growth. In prepubertal children, positive correlations between non-22 kDa GH and weight SDS (r = 0.46; P = 0.03), weight-for-height SDS (r = 0.51; P = 0.01) and body mass index (r = 0.42; P = 0.04) were observed. No significant correlations were seen with spontaneous GH secretion or measurements of IGF-1, IGF-binding protein-3, insulin and leptin. These findings in normal children indicate that the proportion of circulating non-22 kDa GH isoforms may have physiologic significance for growth and metabolism in different stages of development, and emphasize the importance of evaluating the circulating ratio of 22 kDa and non-22 kDa GH in children with growth disorders.
在93名身材正常(身高±2标准差评分)的不同青春期阶段的健康儿童(48名6.8 - 18.4岁男孩和45名3.9 - 18.4岁女孩)中评估了非22 kDa生长激素(GH)异构体的比例。此外,还研究了非22 kDa GH异构体比例、人体测量学、自发性GH分泌和生化指标之间的相关性。血清中非22 kDa GH水平以样本中总GH浓度的百分比表示,通过22 kDa GH排除测定法确定,该方法从血清中去除单体和二聚体22 kDa GH,并使用多克隆抗体GH测定法定量非22 kDa GH异构体。样本选自在24小时GH谱中的自发性GH峰值。对于男孩,非22 kDa GH异构体的中位数比例为8.5%(范围3.2 - 26.6%),女孩为9.6%(1.8 - 17.4%),在青春期前(男孩7.2%;女孩8.8%)或青春期儿童(男孩9.1%;女孩9.9%)中,年龄和性别均无影响。然而,青春期男孩中非22 kDa GH异构体的中位数比例(9.1%)显著高于青春期前男孩(7.2%;P = 0.03)。在青春期男孩中,身高标准差评分(SDS)与非22 kDa GH异构体比例呈负相关(r = -0.38;P = 0.02),尤其是在青春期中期(r = -0.7;P = 0.01),这表明循环中非22 kDa GH异构体数量增加与生长减缓有关。在青春期前儿童中,观察到非22 kDa GH与体重SDS(r = 0.46;P = 0.03)、身高体重比SDS(r = 0.51;P = 0.01)和体重指数(r = 0.42;P = 0.04)之间呈正相关。与自发性GH分泌或胰岛素样生长因子-1(IGF-1)、IGF结合蛋白-3、胰岛素和瘦素的测量值均未发现显著相关性。正常儿童的这些发现表明,循环中非22 kDa GH异构体的比例可能对不同发育阶段的生长和代谢具有生理意义,并强调了评估生长障碍儿童中22 kDa和非22 kDa GH循环比例的重要性。