Potential metabolic mechanism of girls' central precocious puberty: a network analysis on urine metabonomics data. BMC systems biology BACKGROUND:Central precocious puberty (CPP) is a common pediatric endocrine disease caused by early activation of hypothalamic-putuitary-gonadal (HPG) axis, yet the exact mechanism was poorly understood. Although there were some proofs that an altered metabolic profile was involved in CPP, interpreting the biological implications at a systematic level is still in pressing need. To gain a systematic understanding of the biological implications, this paper analyzed the CPP differential urine metabolites from a network point of view. RESULTS:In this study, differential urine metabolites between CPP girls and age-matched normal ones were identified by LC-MS. Their basic topological parameters were calculated in the background network. The network decomposition suggested that CPP differential urine metabolites were most relevant to amino acid metabolism. Further proximity analysis of CPP differential urine metabolites and neuro-endocrine metabolites showed a close relationship between CPP metabolism and neuro-endocrine system. Then the core metabolic network of CPP was successfully constructed among all these differential urine metabolites. As can be demonstrated in the core network, abnormal aromatic amino acid metabolism might influence the activity of HPG and hypothalamic pituitary adrenal (HPA) axis. Several adjustments to the early activation of puberty in CPP girls could also be revealed by urine metabonomics. CONCLUSIONS:The present article demonstrated the ability of urine metabonomics to provide several potential metabolic clues for CPP's mechanism. It was revealed that abnormal metabolism of amino acid, especially aromatic amino acid, might have a close correlation with CPP's pathogenesis by activating HPG axis and suppressing HPA axis. Such a method of network-based analysis could also be applied to other metabonomics analysis to provide an overall perspective at a systematic level. 10.1186/1752-0509-6-S3-S19

Serum metabolomic analysis reveals key metabolites in drug treatment of central precocious puberty in female children. Frontiers in molecular neuroscience 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. 10.3389/fnmol.2022.972297