title: Effects of Long-Term In Vivo Exposure to Di-2-Ethylhexylphthalate on Thyroid Hormones and the TSH/TSHR Signaling Pathways in Wistar Rats.
abstract: Di-(2-ethylhexyl)phthalate (DEHP) was a widely used chemical with human toxicity. Recent in vivo and in vitro studies suggested that DEHP-exposure may be associated with altered serum thyroid hormones (THs) levels, but the underlying molecular mechanisms were largely unknown. To explore the possible molecular mechanisms, 128 Wistar rats were dosed with DEHP by gavage at 0, 150, 300, and 600 mg/kg/day for 3 months (M) and 6 M, respectively. After exposure, expression of genes and proteins in the thyroid, pituitary, and hypothalamus tissues of rats were analyzed by Q-PCR and western blot, while the sera and urine samples were assayed by radioimmunoassay and ELISA. Results showed that serum THs levels were suppressed by DEHP on the whole. DEHP treatment influenced the levels of rats' thyrotropin releasing hormone receptor (TRHr), Deiodinases 1 (D1), thyroid stimulating hormone beta (TSHβ), sodium iodide symporter (NIS), thyroid stimulating hormone receptor (TSHr), thyroperoxidase (TPO), thyroid transcription factor 1 (TTF-1), and thyroglobulin (TG) mRNA/protein expression in the hypothalamus-pituitary-thyroid (HPT) axis and decreased urine iodine. Taken together, observed findings indicate that DEHP could reduce thyroid hormones via disturbing the HPT axis, and the activated TSH/TSHR pathway is required to regulate thyroid function via altering TRHr, TSHβ, NIS, TSHr, TPO, TTF-1 and TG mRNA/protein expression of the HPT axis.
authors.affiliation: Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China. dongxinwen118@yeah.net.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China. dongjin1992dj@sina.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China. zy244943459@163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China. guojipeng90@163.com.
authors.forename: Jipeng
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China. wangzhanju00@163.com.
authors.forename: Zhanju
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China. liumingqihlj@163.com.
authors.forename: Mingqi
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China. zhangyunbo1982@126.com.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China. naxiaolin1495@sohu.com.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Na
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000187:drug effects*; D007453:Iodide Peroxidase / Q000187:drug effects; D033862:Iron-Binding Proteins / Q000187:drug effects; D009687:Nuclear Proteins / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects*; D010907:Pituitary Hormones / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000187:drug effects*; D013963:Thyroid Hormones / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects
chemical_list: D001324:Autoantigens; D033862:Iron-Binding Proteins; C000614412:NKX2-1 protein, human; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D010907:Pituitary Hormones; D013963:Thyroid Hormones; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D013972:Thyrotropin; D004051:Diethylhexyl Phthalate; C056658:TPO protein, human; D007453:Iodide Peroxidase
keywords: DEHP; TSH/TSHR; hypothalamus-pituitary-thyroid axis; molecular mechanisms; signaling pathways; thyroid function