Woelfle J F, Harz K, Roth C
Children's Hospital, University of Bonn, Bonn, Germany.
Exp Clin Endocrinol Diabetes. 2007 Jan;115(1):17-23. doi: 10.1055/s-2006-957350.
Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are key factors in the control of somatic growth. Recent work revealed a critical role for the transcription factor STAT5b in GH stimulated IGF-I gene expression. In obesity, the normal regulation of the GH/IGF-I axis is disturbed, with normal levels of circulating IGF-I despite blunted GH secretion. We hypothesized that leptin or other hormonal regulators of energy homeostasis, which can activate Stat5b-regulated gene expression or exert an effect on GH secretion, might be able to substitute for GH in terms of IGF-I synthesis. Thus, the aim of this study was to identify potential regulators of IGF-I serum levels in obesity with a particular focus on the interaction of leptin and IGF-I. In a cross-sectional study, we measured hormonal and auxiological parameters in 99 obese children who were referred to our obesity outpatient clinic and analysed correlations between unadjusted hormone levels and between hormone concentrations expressed as SDS values, adjusted for sex, age, and/or puberty and BMI. Serum concentrations of IGF-I correlated highly significant with IGFBP-3, leptin, fasting ghrelin and insulin (p<0.001). However, when expressing hormone levels as SDS values, only leptin SDS and IGFBP-3 SDS correlated significantly with IGF-I SDS (p<0.01). This correlation between leptin SDS and IGF-I SDS was more pronounced in prepubertal and in male subjects, with increasing IGF-I SDS values paralleling an increase in leptin SDS tertiles in prepubertal subjects. In linear regression analyses, leptin SDS, IGFBP-3 SDS and BMI SDS contributed significantly to the variation of IGF-I SDS values, and explained 53.3% of the variability of IGF-I SDS levels in male subjects.
In summary, we demonstrated a strong correlation of age and sex-adjusted standard deviation scores (SDS) for IGF-I and leptin in obese children, which is modulated by sex, pubertal stage and body weight. Whether this association results from a direct induction of hepatic IGF-I gene expression by leptin or reflects a more complex interrelationship between IGF-I and obesity-related factors should be subject of future research.
生长激素（GH）和胰岛素样生长因子-I（IGF-I）是控制躯体生长的关键因素。近期研究揭示了转录因子STAT5b在GH刺激的IGF-I基因表达中起关键作用。在肥胖症中，GH/IGF-I轴的正常调节受到干扰，尽管GH分泌减弱，但循环中的IGF-I水平正常。我们推测，瘦素或其他能量稳态的激素调节因子，能够激活Stat5b调节的基因表达或对GH分泌产生影响，在IGF-I合成方面可能能够替代GH。因此，本研究的目的是确定肥胖症中IGF-I血清水平的潜在调节因子，特别关注瘦素与IGF-I的相互作用。在一项横断面研究中，我们测量了99名转诊至我们肥胖门诊的肥胖儿童的激素和人体测量学参数，并分析了未调整的激素水平之间以及经性别、年龄和/或青春期及BMI调整后以SDS值表示的激素浓度之间的相关性。IGF-I的血清浓度与IGFBP-3、瘦素、空腹胃饥饿素和胰岛素高度显著相关（p<0.001）。然而，当以SDS值表示激素水平时，只有瘦素SDS和IGFBP-3 SDS与IGF-I SDS显著相关（p<0.01）。瘦素SDS与IGF-I SDS之间的这种相关性在青春期前和男性受试者中更为明显，青春期前受试者中IGF-I SDS值的增加与瘦素SDS三分位数的增加平行。在线性回归分析中，瘦素SDS、IGFBP-3 SDS和BMI SDS对IGF-I SDS值的变化有显著贡献，并解释了男性受试者中IGF-I SDS水平变异性的53.3%。
总之，我们证明了肥胖儿童中经年龄和性别调整的IGF-I和瘦素标准差评分（SDS）之间存在强相关性，这种相关性受性别、青春期阶段和体重的调节。这种关联是瘦素直接诱导肝脏IGF-I基因表达的结果，还是反映了IGF-I与肥胖相关因素之间更复杂的相互关系，应是未来研究的主题。
