Göteborg Pediatric Growth Research Center (GP-GRC), The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Clin Endocrinol (Oxf). 2013 Nov;79(5):675-82. doi: 10.1111/cen.12196. Epub 2013 Apr 11.
A high-throughput pharmaco-proteomic approach has previously been successfully used to identify lipoprotein biomarkers related to changes in longitudinal growth and bone mass in response to growth hormone (GH) treatment. The aim of this study was to identify protein markers involved in the diverse anabolic and lipolytic remodelling of body composition during GH treatment.
DESIGN, PATIENTS AND MEASUREMENTS: The study population consisted of 128 prepubertal children receiving GH treatment. Thirty-nine were short as a result of GH deficiency, and 89 had idiopathic short stature (ISS). Serum protein expression profiles at study start and after 1 year of GH treatment were analysed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Body composition was analysed by dual-energy X-ray absorptiometry (DXA), reliably estimating muscle mass from appendicular (arms and legs) lean soft tissue mass (LST). DXA was also used to estimate appendicular bone mineral content (BMC) and fat mass for the total body.
Specific protein expression patterns associated with GH response in different body compartments were identified. Among identified proteins, different isoforms of nutrition markers such as apolipoproteins (Apo) were recognized: Apo C-I, Apo A-II, serum amyloid A4 (SAA4) and transthyretin (TTR). In addition, unidentified peaks were associated with GH effects on specific body compartments.
Our results suggest that unique protein markers are associated with remodelling of different body compartments during GH treatment, which in the future might be useful to optimize GH treatment not only with regard to longitudinal growth.
高通量药物蛋白质组学方法已成功用于鉴定与生长激素 (GH) 治疗引起的纵向生长和骨量变化相关的脂蛋白生物标志物。本研究旨在鉴定参与 GH 治疗期间身体成分的不同合成代谢和脂肪分解重塑的蛋白质标记物。
设计、患者和测量：研究人群包括 128 名接受 GH 治疗的青春期前儿童。39 名因 GH 缺乏而身材矮小，89 名患有特发性身材矮小 (ISS)。使用表面增强激光解吸/电离飞行时间质谱 (SELDI-TOF MS) 分析研究开始时和 GH 治疗 1 年后的血清蛋白表达谱。使用双能 X 射线吸收法 (DXA) 分析身体成分，从四肢（手臂和腿部）的瘦软组织质量 (LST) 可靠估计肌肉质量。DXA 还用于估计全身的四肢骨矿物质含量 (BMC) 和脂肪量。
确定了与不同身体部位 GH 反应相关的特定蛋白表达模式。在所鉴定的蛋白中，识别出了不同的营养标志物同工型，如载脂蛋白 (Apo)：Apo C-I、Apo A-II、血清淀粉样蛋白 A4 (SAA4) 和转甲状腺素蛋白 (TTR)。此外，未识别的峰与 GH 对特定身体部位的作用有关。
我们的结果表明，在 GH 治疗期间，不同身体部位的重塑与独特的蛋白质标记物相关，这可能有助于将来不仅优化纵向生长的 GH 治疗。
