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胚胎液中胰岛素样生长因子结合蛋白浓度及翻译后修饰

Insulin-like growth factor binding protein concentration and post-translational modification in embryological fluid.

作者信息

Miell J P, Jauniaux E, Langford K S, Westwood M, White A, Jones J S

机构信息

Academic Department of Medicine, King's College School of Medicine and Dentistry, London, UK.

出版信息

Mol Hum Reprod. 1997 Apr;3(4):343-9. doi: 10.1093/molehr/3.4.343.

DOI:10.1093/molehr/3.4.343
PMID:9237262
Abstract

Levels of proteolytic activity directed against insulin-like growth factor binding protein 3 (IGFBP-3) and the distribution of phosphorylated isoforms of IGFBP-1 were assessed in matched sample sets of maternal serum, coelomic fluid and amniotic fluid from 21 pregnancies at 6-12 weeks gestation. In addition, concentrations of immunoreactive IGFBP-1 to -3, insulin-like growth factor (IGF)-I and -II were determined in all three compartments in 21 pregnancies, and in coelomic fluid and maternal serum in 58 pregnancies. IGF-I concentrations were highest in maternal serum and similarly low in coelomic and amniotic fluid. IGF-II concentrations were also highest in maternal serum but easily detectable in coelomic fluid where concentrations showed a significant correlation with gestational age. IGFBP-1 concentrations were higher in coelomic fluid than in either maternal serum or amniotic fluid and showed a significant correlation with gestational age in this compartment. Analysis of IGFBP-1 phosphoforms showed clear differences in phosphorylation of IGFBP-1 between groups with maternal serum containing predominantly the phosphorylated forms and coelomic fluid almost exclusively the non-phosphorylated form. First trimester amniotic fluid IGFBP-1 was barely detectable and appeared non-phosphorylated. These findings suggest that the high IGF-II concentrations and lack of inhibitory phosphoforms of IGFBP-1 in coelomic fluid could potentially enhance mitogenic activity in the early human gestational sac. IGFBP-2 concentrations were high in coelomic fluid compared with maternal serum whereas coelomic fluid IGFBP-3 concentrations were intermediate, easily detectable and correlated strongly with gestational age. Protease activity was far less in coelomic fluid than in matched maternal serum samples. Marked differences in both concentrations and post-translational modification of IGFBPs in maternal serum compared with embryonic fluid suggest different regulatory pathways.

摘要

在妊娠6至12周的21例孕妇的配对样本组中,评估了针对胰岛素样生长因子结合蛋白3(IGFBP-3)的蛋白水解活性水平以及IGFBP-1磷酸化异构体的分布。此外,测定了21例孕妇所有三个腔室以及58例孕妇体腔液和母血中免疫反应性IGFBP-1至-3、胰岛素样生长因子(IGF)-I和-II的浓度。IGF-I浓度在母血中最高,在体腔液和羊水中同样较低。IGF-II浓度在母血中也最高,但在体腔液中易于检测到,其浓度与孕周呈显著相关。体腔液中IGFBP-1浓度高于母血或羊水,且在该腔室中与孕周呈显著相关。IGFBP-1磷酸化形式的分析显示,各组之间IGFBP-1的磷酸化存在明显差异,母血中主要含有磷酸化形式,而体腔液中几乎只含有非磷酸化形式。孕早期羊水IGFBP-1几乎检测不到,且似乎未磷酸化。这些发现表明,体腔液中高浓度的IGF-II和缺乏IGFBP-1的抑制性磷酸化形式可能会增强人早期妊娠囊中的促有丝分裂活性。与母血相比,体腔液中IGFBP-2浓度较高,而体腔液中IGFBP-3浓度处于中等水平,易于检测且与孕周密切相关。体腔液中的蛋白酶活性远低于配对的母血样本。与胚胎液相比,母血中IGFBPs在浓度和翻译后修饰方面的显著差异表明存在不同的调节途径。

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