Urinary metabolite markers of precocious puberty.
The incidence of precocious puberty (PP, the appearance of signs of pubertal development 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) 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 and gas chromatography-time of flight mass spectrometry. 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 provided 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 activation of the sympathetic nervous system and the hypothalamic-pituitary-gonadal axis. 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.
Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Ying
Y
Qi
Children's Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
Pin
P
Li
Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: dryyz@sina.com.
Yongyu
Y
Zhang
Children's Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
Lulu
L
Cui
Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Zi
Z
Guo
Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina 28081. Electronic address: g_xie@uncg.edu.
Guoxiang
G
Xie
David H. Murdock Research Institute, North Carolina Research Campus, Kannapolis, North Carolina 28081.
Mingming
M
Su
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Xin
X
Li
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Xiaojiao
X
Zheng
Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina 28081.
Yunping
Y
Qiu
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Yumin
Y
Liu
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Aihua
A
Zhao
Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Weiping
W
Jia
Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina 28081. Electronic address: w_jia@uncg.edu.
Wei
W
Jia
D015415:Biomarkers / Q000652:urine*; D002648:Child; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006728:Hormones / Q000652:urine; D006801:Humans; D055442:Metabolome; D011629:Puberty, Precocious / Q000188:drug therapy / Q000652:urine*; D017329:Triptorelin Pamoate / Q000627:therapeutic use
D015415:Biomarkers; D006728:Hormones; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone