Powell D R, Durham S K, Liu F, Baker B K, Lee P D, Watkins S L, Campbell P G, Brewer E D, Hintz R L, Hogg R J
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
J Clin Endocrinol Metab. 1998 May;83(5):1654-61. doi: 10.1210/jcem.83.5.4755.
Children with chronic renal failure (CRF) are often growth recarded despite normal serum levels of GH and insulin-like growth factors (IGFs). Recent studies suggest that excess IGF-binding proteins (IGFBPs) in the 35-kDa fractions of CRF serum contribute to CRF growth failure. This report characterizes the relationship between IGFBP-3 and IGF peptides in the serum of growth-retarded CRF children. Size-exclusion chromatography at pH 7.4 found IGFBP-3 and IGFs almost exclusively in the 150-kDa fractions of normal serum, where their molar stoichiometry was approximately 1:1. However, similar chromatography of CRF serum found a molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions and large amounts of IGFs in the 35-kDa fractions. In the 150-kDa fractions of CRF serum, IGFBP-3 was present in normal amounts, but a greater than normal amount was in the form of a 29-kDa IGFBP-3 fragment. Treatment of these CRF children with recombinant human GH increased the molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions, the amount of IGFBP-3 and total IGFs in the 150-kDa fractions, and the amount of IGFs, but not IGFBPs, in the 35-kDa fractions. These data suggest that in untreated CRF children, proteolysis of IGFBP-3 in the 150-kDa fractions releases IGFs to the excess IGFBPs in the 35-kDa fractions, but insufficient IGF is released to overcome the growth-inhibiting effects of these excess IGFBPs. Treatment with recombinant human GH increases levels of IGFs and IGFBP-3 in the 150-kDa fractions, and subsequent IGFBP-3 proteolysis releases sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the 35-kDa fractions of CRF serum.
尽管慢性肾衰竭（CRF）患儿血清生长激素（GH）和胰岛素样生长因子（IGF）水平正常，但他们往往生长迟缓。最近的研究表明，CRF患儿血清35 kDa组分中过量的胰岛素样生长因子结合蛋白（IGFBP）导致了CRF生长障碍。本报告描述了生长迟缓的CRF患儿血清中IGFBP-3与IGF肽之间的关系。在pH 7.4条件下进行的尺寸排阻色谱分析发现，IGFBP-3和IGF几乎仅存在于正常血清的150 kDa组分中，其摩尔化学计量比约为1:1。然而，对CRF患儿血清进行类似的色谱分析发现，150 kDa组分中IGFBP-3的摩尔量超过总IGF，且35 kDa组分中有大量IGF。在CRF患儿血清的150 kDa组分中，IGFBP-3含量正常，但大于正常量的部分以29 kDa的IGFBP-3片段形式存在。用重组人生长激素治疗这些CRF患儿，会增加150 kDa组分中IGFBP-3相对于总IGF的摩尔过量、150 kDa组分中IGFBP-3和总IGF的含量，以及35 kDa组分中IGF（而非IGFBP）的含量。这些数据表明，在未经治疗的CRF患儿中，150 kDa组分中IGFBP-3的蛋白水解作用将IGF释放到35 kDa组分中过量的IGFBP中，但释放的IGF不足以克服这些过量IGFBP的生长抑制作用。用重组人生长激素治疗可提高150 kDa组分中IGF和IGFBP-3的水平，随后IGFBP-3的蛋白水解作用释放出足够的IGF，以克服CRF患儿血清35 kDa组分中过量IGFBP的生长抑制作用。
