Table_2_Serum metabolomic analysis reveals key metabolites in drug treatment of central precocious puberty in female children.XLSX

Precocious puberty (PP) is a common condition among children. According to the pathogenesis and clinical manifestations, PP can be divided into central precocious puberty (CPP, gonadotropin dependent), peripheral precocious puberty (PPP, gonadotropin independent), and incomplete precocious puberty (IPP). Identification of the variations in key metabolites involved in CPP and their underlying biological mechanisms has increased the understanding of the pathological processes of this condition. However, little is known about the role of metabolite variations in the drug treatment of CPP. Moreover, it remains unclear whether the understanding of the crucial metabolites and pathways can help predict disease progression after pharmacological therapy of CPP. In this study, systematic metabolomic analysis was used to examine three groups, namely, healthy control (group N, 30 healthy female children), CPP (group S, 31 female children with CPP), and treatment (group R, 29 female children) groups. A total of 14 pathways (the top two pathways were aminoacyl–tRNA biosynthesis and phenylalanine, tyrosine, and tryptophan biosynthesis) were significantly enriched in children with CPP. In addition, two short peptides (His-Arg-Lys-Glu and Lys-Met-His) were found to play a significant role in CPP. Various metabolites associated with different pathways including amino acids, PE [19:1(9Z)0:0], tumonoic acid I, palmitic amide, and linoleic acid–biotin were investigated in the serum of children in all groups. A total of 45 metabolites were found to interact with a chemical drug [a gonadotropin-releasing hormone (GnRH) analog] and a traditional Chinese medicinal formula (DBYW). This study helps to understand metabolic variations in CPP after drug therapy, and further investigation may help develop individualized treatment approaches for CPP in clinical practice.

性早熟（Precocious Puberty, PP）是儿童群体中常见的病症。依据发病机制与临床表现，性早熟可分为中枢性性早熟（Central Precocious Puberty, CPP，促性腺激素依赖性）、外周性性早熟（Peripheral Precocious Puberty, PPP，非促性腺激素依赖性）以及不完全性性早熟（Incomplete Precocious Puberty, IPP）。明确中枢性性早熟相关关键代谢物的变异及其潜在生物学机制，有助于加深对该病症病理进程的认知。然而，目前对于代谢物变异在中枢性性早熟药物治疗中的作用仍知之甚少。此外，目前尚不清楚对关键代谢物及代谢通路的认知，能否用于预测中枢性性早熟药物治疗后的疾病进展情况。本研究采用系统性代谢组学分析方法，对三组受试对象展开研究：健康对照组（N组，30名健康女童）、中枢性性早熟组（S组，31名确诊中枢性性早熟的女童）以及治疗组（R组，29名女童）。中枢性性早熟患儿中共显著富集了14条代谢通路，其中排名前两位的通路为氨酰-tRNA生物合成通路以及苯丙氨酸、酪氨酸与色氨酸生物合成通路。此外，本研究还发现两条短肽（组氨酸-精氨酸-赖氨酸-谷氨酸（His-Arg-Lys-Glu）与赖氨酸-甲硫氨酸-组氨酸（Lys-Met-His））在中枢性性早熟中发挥重要作用。本研究对所有受试儿童血清中的多种代谢物进行了检测，这些代谢物关联多条代谢通路，包括氨基酸类、磷脂酰乙醇胺（PE）[19:1(9Z)0:0]、土莫诺酸I（tumonoic acid I）、棕榈酰胺以及亚油酸-生物素缀合物等。研究发现，共有45种代谢物可与一种化学药物（促性腺激素释放激素（GnRH）类似物）以及一种中药方剂（DBYW）发生相互作用。本研究有助于阐明中枢性性早熟药物治疗后的代谢变异情况，后续进一步研究或可助力临床中枢性性早熟个体化治疗方案的开发。