title: Endocrine disrupting chemicals affect the gonadotropin releasing hormone neuronal network.
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.
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Johanna K
authors.initials: JK
authors.lastname: Mueller
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany; Children's Hospital "Auf der Bult", Hannover, Germany. Electronic address: Heger@hka.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Heger
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity; D002460:Cell Line; D002478:Cells, Cultured; D052244:Endocrine Disruptors / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D019833:Genistein / Q000633:toxicity; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D006801:Humans; D007031:Hypothalamus / Q000166:cytology; D059648:Kisspeptins / Q000235:genetics*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000633:toxicity; D048789:Phytoestrogens / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D011401:Promoter Regions, Genetic; D017207:Rats, Sprague-Dawley; D064249:Securin / Q000235:genetics*; D050986:YY1 Transcription Factor / Q000235:genetics; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D019833:Genistein; D007987:Gonadotropin-Releasing Hormone; D059648:Kisspeptins; D010636:Phenols; D048789:Phytoestrogens; D000072317:Polychlorinated Dibenzodioxins; D064249:Securin; D050986:YY1 Transcription Factor; C106628:KISS1 protein, human; C494700:Yy1 protein, rat; C578002:pituitary tumor-transforming protein 1, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: EAP1; Endocrine disrupting chemicals; KiSS1; Puberty; Transcription