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Phthalate Exposure May Affect Girl Puberty Via Stimulation of Kisspeptin-54 Secretion

Chen, Chung-Yu1; Wu, Yu-Min1; Chou, Yen-Yin2; Lin, Shio-Jean2; Lee, Ching-Chang1,3

doi: 10.1097/01.ede.0000392060.55344.46
Abstracts: ISEE 22nd Annual Conference, Seoul, Korea, 28 August–1 September 2010: Chemicals and Environmental Health Issues: Phthalate Exposure

1Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan; and 3Research Center of Environmental Trace Toxic Substance, National Cheng Kung University, Tainan, Taiwan.

Abstracts published in Epidemiology have been reviewed by the societies at whose meetings the abstracts have been accepted for presentation. These abstracts have not undergone review by the Editorial Board of Epidemiology.


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Central precocious puberty (CPP) is a complex problem with hypothalamic-pituitary-gonadal (HPG) axis for children development. This research is aimed to investigate the relationship and effect mechanism between phthalate exposure and girl puberty.

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This case-control study was conducted from 2007 to 2009. Twenty-six CPP girls were recruited from the polyclinic of Pediatric Endocrinology in National Cheng Kung University Hospital, and 11 normal and similar age ranged girls were recruited as control group from elementary school. Informed consents were obtained from all participants and their parents. Basic clinical diagnostic, luteinizing hormone, follicle-stimulating hormone, estradiol, 7 urinary phthalate metabolites, and kisspeptin-54 levels were evaluated in each participant. The concentration of kisspeptin-54 was measured using kisspeptin-54 radioimmunoassay kit. Seven urinary phthalate metabolites including MMP, MEP, MBP, MBzP, MEHP, MEOHP, and MEHHP were analyzed by LC-MS/MS.

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Kisspeptin-54 levels of CPP girls were significantly higher than those of control group (2.23 pmol/L V.S. 1.95 pmol/L; P = 0.01). We further divided CPP girls into 2 groups: treatment with Leupline and nontreatment with Leupline. The results showed a significantly increasing trend of kisspeptin-54 among 3 groups (trend test, P = 0.003). Levels of urinary phthalate metabolites also revealed a significant difference (P < 0.05) among 3 groups on MMP, MBP, MBzP, MEOHP, MEHHP. Significantly positive correlation between kisspeptin-54 secretion and urinary MBP levels in girls were found (R 2 = 0.288; P = 0.001).

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In this study, we found MBP may affect puberty onset in girls by stimulating kisspeptin-54 secretion. Future researches are needed to elucidate the mechanism of action and to investigate whether any other factors related to DBP exposure alter the kisspeptin-54 secretion.

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