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.