The PI3K/Akt and ERK pathways elevate thyroid hormone receptor ß1 and TRH receptor to decrease thyroid hormones after exposure to PCB153 and p,p'-DDE.
Chemosphere
; 118: 229-38, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25278044
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 ß1 (TRß1) 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 TRß1 and TRHr and then decrease TH levels, and that would be a potential mechanism by which PCBs and DDT disturb TH homeostasis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Hormônios Tireóideos
/
Bifenilos Policlorados
/
Receptores do Hormônio Liberador da Tireotropina
/
Fosfatidilinositol 3-Quinases
/
Sistema de Sinalização das MAP Quinases
/
Diclorodifenil Dicloroetileno
/
Receptores beta dos Hormônios Tireóideos
/
Proteínas Proto-Oncogênicas c-akt
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article