Endocrine disrupting chemicals affect the Gonadotropin releasing hormone neuronal network |
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| Affiliation: | 1. Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany;2. Children''s Hospital “Auf der Bult”, Hannover, Germany;1. Department of Nutrition and Food Safety, School of Public Heath, Jilin University, 1163 Xin Min Street, Changchun 130021, China;2. Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd, Fengtai District, Beijing 100071, China;1. Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of Macau, Taipa, Macau, China;2. School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China;3. School of Biological Sciences, University of Hong Kong, Pokfulam Road, Hong Kong, China;1. Laboratory of Environmental Medicine and Developmental Toxicology, and Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, China;2. Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, China |
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| Abstract: | Endocrine disrupting chemicals have been shown to alter the pubertal process. The controlling levels of the Gonadotropin releasing hormone (GnRH) network involve GnRH itself, KiSS1, and the transcriptional regulators enhanced at puberty 1 (EAP1), Thyroid Transcription Factor 1 (TTF1), and Yin Yang 1 (YY1). While Genistein and Bisphenol A (BPA) have been shown to advance the advent of puberty, exposure to Dioxin delayed pubertal onset.Utilizing in vitro approaches, we observed that Genistein and BPA suppress inhibitory and activate stimulatory components of the GnRH network, while Dioxin exhibit an inhibitory effect at all regulatory hierarchical levels of the GnRH network. It repressed KiSS1, Gnrh, Ttf1 and Yy1 transcription via the xenobiotic response element (XRE), while EAP1 was not affected.Therefore, EDCs alter the neuroendocrine GnRH regulatory network at all hierarchical levels. |
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| Keywords: | Puberty Endocrine disrupting chemicals Transcription KiSS1 EAP1 |
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