Potential metabolic mechanism of girls' central precocious puberty: a network analysis on urine metabonomics data

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.

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.

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.