JNK pathway decreases thyroid hormones via TRH receptor: a novel mechanism for disturbance of thyroid hormone homeostasis by PCB153.
PCBs, widespread and well-characterized endocrine disruptors, cause the disruption of thyroid hormone (TH) homeostasis in humans and animals. In order to verify the hypotheses that MAPK pathways would play roles in disturbance of TH levels caused by PCBs, and that TH-associated receptors could function in certain MAPK pathway, Sprague-Dawley rats were dosed with PCB153 intraperitoneally (i.p.) at 0, 4, 16 and 32mg/kg for 5 consecutive days, and Nthy-ori 3-1 cells were treated with PCB153 (0, 1, 5, 10μM) for 30min. Results showed that after the treatment with PCB153, serum total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3) and thyrotropin releasing hormone (TRH) were decreased, whereas free triiodothyronine (FT3) and serum thyroid stimulating hormone (TSH) were not altered. In vivo and in vitro studies indicated that JNK pathway was activated after PCB153 exposure. Moreover, TRH receptor (TRHr) level was suppressed after the activation of JNK pathway and was elevated after the inhibition of JNK pathway, but TSH receptor (TSHr) level was not affected by the status of JNK pathway though it was reduced after PCB153 treatment. The activated signs of ERK and P38 pathways were not observed in this study. Taken together, observed effects suggested that JNK pathway could decrease TH levels via TRHr, and that would be one novel mechanism of PCB153-mediated disruption of THs.
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, 13 Hangkong Road, Wuhan 430030, PR China.
Changjiang
C
Liu
Mei
M
Ha
Yushan
Y
Cui
Chengmin
C
Wang
Maosheng
M
Yan
Wenjuan
W
Fu
Chao
C
Quan
Jun
J
Zhou
Kedi
K
Yang
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000097:blood*; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*
D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D011078:Polychlorinated Biphenyls; D048031:JNK Mitogen-Activated Protein Kinases; D013974:Thyroxine; C014024:2,4,5,2',4',5'-hexachlorobiphenyl