性早熟女童多条代谢途径和激素水平异于正常

　　上海中医药大学和上海交大附属儿童医院的一项最新合作研究发现，性早熟女童的代谢模式与正常女童存在明显差异，且体重偏重，并首次报道了肠道菌群参与性早熟的发病过程，以及代谢组学方法在疾病诊断方面的应用前景，这些研究结果为剖析中医药治疗性早熟提供了潜靶点。

性发育提前有隐患

　　据悉，在全球范围内，性发育提前已是不争的事实，根据北卡罗莱纳大学科学家对三个城市1200名女童的调查，黑人女童在8岁时乳房发育到第二期的比例达43%，白人和西班牙裔8岁女童的比例分别为18%和31%。我国内地的发病率，从十年前的0.5%到现今的5%，也呈现着快速增长趋势。

　　性早熟已经在全球范围内引起儿科专家和公共卫生专家的重视。女孩过早出现乳房发育，甚至月经来潮，而智力和性心理尚未成熟，容易发生社会问题，也给家长造成精神和生活上的负担。另一方面，在性征提早出现的同时，往往伴有骨骼生长加速，患儿虽暂时较同龄小儿高，但由于骨骺提前闭合，成年后身材往往比正常人矮小。典型的真性性早熟患儿，约有半数最终身高不足150厘米。

6种激素与发病相关

　　上海中医药大学中医方证与系统生物学研究中心张永煜教授、贾伟教授，上海交通大学附属儿童医院的科研人员合作研究，发现性早熟女童的代谢模式与正常女童存在明显差异，且体重偏重，进一步研究发现女童性早熟发病过程与色氨酸、酪氨酸、三羧酸循环等多条代谢通路发生改变直接相关。

　　实验中还检测到6种与性早熟发病相关的激素，尤其是催乳素（prolactin）、促黄体生成素（lu－teotropic hormone，LH）、卵泡刺激素（follicle-stimulating hormone,FSH）、雌二醇（Estradiol,E2）与健康女童相比分别增高了0.7、1.5、1.6和11.5倍。并首次报道了肠道菌群参与性早熟的发病过程，以及代谢组学方法在疾病诊断方面的应用前景。这些研究结果还为剖析中医药治疗性早熟提供了潜靶点。

　　该研究得到国家自然科学基金和上海市教委“085”学科内涵建设经费资助，研究成果于2011年10月25日在国际权威期刊《分子与细胞蛋白质组学》（Molecular and Cellular Proteomics）杂志上在线刊出，受到业内高度关注和评价。

原文阅读：

Urinary metabolite markers of precocious puberty

Ying Qi, Pin Li, Yongyu Zhang, Lulu Cui, Zi Guo, Guoxiang Xie, Mingming Su, Xin Li, Xiaojiao Zheng, Yunping Qiu, Yumin Liu, Aihua Zhao, Weiping Jia and Wei Jia

　　The incidence of precocious puberty (PP, the appearance of signs of pubertal de-velopment at an abnormally early age), is rapidly rising, concurrent with changes of diet, lifestyles and social environment. The current diagnostic methods are based on a hormone (gonadotropin-releasing hormone, GnRH) stimulation test, which is costly, time-consuming and uncomfortable for patients. The lack of molecular biomarkers to support simple laboratory tests, such as a blood or urine test, has been a long-standing bottleneck in the clinical diagnosis and evaluation of PP. Here we report a metabolomic study using an ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-QTOFMS) and gas chromatography-time of flight mass spectrometry (GC-TOFMS). Urine metabolites from 163 individuals were profiled and the metabolic alterations were analyzed after treatment of central precocious puberty (CPP) with Triptorelin depot. A panel of biomarkers selected from >70 differentially expressed urinary metabolites by receiver operating characteristic and logistic regression analysis provide excellent predictive power with high sensitivity and specificity for PP. The altered metabolic profile of the PP patients was characterized by three major perturbed metabolic pathways, catecholamine, serotonin metabolism and tricarboxylic acid cycle, presumably resulting from an activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary-gonadal axis (HPGA). The treatment with Triptorelin depot was able to normalize these three altered pathways. Additionally, significant changes in the urine levels of 4-hydroxyphenylacetic acid, 5-hydroxyindoleacetic acid, indoleacetic acid, 5-hydroxytryptophan and 5-hydroxykynurenamine in the CPP group suggest that the development of CPP condition may involve an alteration in symbiotic gut microbial composition.

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