title: The PI3K/Akt and ERK pathways elevate thyroid hormone receptor β1 and TRH receptor to decrease thyroid hormones after exposure to PCB153 and p,p'-DDE.
abstract: PCBs and DDT cause the disturbance of thyroid hormone (TH) homeostasis in humans and animals. To test the hypothesis that the PI3K/Akt and MAPK pathways would play significant roles in TH imbalance caused by PCBs and DDT, Sprague-Dawley rats were dosed with PCB153 and p,p'-DDE intraperitoneally for 5 consecutive days, and human thyroid follicular epithelial (Nthy-ori 3-1 cell line) were treated with PCB153 and p,p'-DDE for different time. Results showed that serum total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3) and thyroid stimulating hormone (TSH) were decreased, whereas serum free triiodothyronine (FT3) and thyrotropin releasing hormone (TRH) were not changed. The PI3K/Akt and ERK pathways were activated in vivo and in vitro after the treatment with PCB153 and p,p'-DDE. Moreover, TH receptor β1 (TRβ1) was elevated after the activation of the PI3K/Akt pathway and was depressed after the inhibition of the PI3K/Akt pathway; TRH receptor (TRHr) was increased after the activation of the ERK pathway and was decreased after the inhibition of the ERK pathway. Though TH receptor α1 (TRα1) level was increased in the hypothalamus, TRα1 and TSHr were not influenced by the status of signaling pathways in in vitro study. Taken together, after exposure to PCB153 and p,p'-DDE, activated PI3K/Akt and ERK pathways disrupt the hypothalamic-pituitary-thyroid (HPT) axis via TRβ1 and TRHr and then decrease TH levels, and that would be a potential mechanism by which PCBs and DDT disturb TH homeostasis.
authors.affiliation: MOE Key Lab of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China; Key Lab of Birth Defects and Reproductive Health of National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing 400020, PR China.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Lab of Birth Defects and Reproductive Health of National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing 400020, PR China.
authors.forename: Lianbing
authors.initials: L
authors.lastname: Li
authors.affiliation: Chongqing Three Gorges Medical College, Chongqing 400020, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Ha
authors.affiliation: MOE Key Lab of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Suqin
authors.initials: S
authors.lastname: Qi
authors.affiliation: MOE Key Lab of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Duan
authors.affiliation: MOE Key Lab of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: cj_514@163.com.
authors.forename: Kedi
authors.initials: K
authors.lastname: Yang
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000378:metabolism*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism*; D013963:Thyroid Hormones / Q000097:blood* / Q000378:metabolism
chemical_list: D018025:Receptors, Thyrotropin-Releasing Hormone; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D003633:Dichlorodiphenyl Dichloroethylene; D011078:Polychlorinated Biphenyls; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C014024:2,4,5,2',4',5'-hexachlorobiphenyl
keywords: ERK; PCB153; PI3K/Akt; Thyroid hormone receptor β1; Thyrotropin releasing hormone receptor; p,p′-DDE