Differential regulation of thyroid hormone receptor-mediated function by endocrine disruptors.
It is well known that endocrine disruptors (EDs) act as anti-estrogenic agents and affect the function of reproductive organ. EDs are also thought to affect thyroid hormone (TH) system which is important for biological functions such as growth, development and metabolism. However, it is still not clear how EDs are able to regulate TH receptor (TR)-mediated functions. In this study, therefore, the modulatory effects of representative EDs such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyl (Aroclor 1254) and bisphenol A (BPA) were examined using TR-expressing GH3 cells (a rat pituitary gland epithelial tumor cell line) activated by triiodothyronine (T3). EDs tested significantly blocked T3 binding to TR in a dose-dependent manner. Biochemical characterization by Scatchard and Lineweaver-Burk plot analyses indicated that TCDD and aroclor 1254 bound to TH receptors in a competitive inhibitory manner, whereas BPA bound to TH receptors in a non-competitive pattern. The different inhibitory mode of action by EDs was also found in regulating TR-mediated production of prolactin (PRL). Aroclor 1254 exposure for 48 h enhanced T3-mediated PRL production, but BPA down-regulated. These results suggest that the EDs (TCDD, Aroclor 1254 and BPA) could differentially bind to TR and distinctly regulate the action of TR function, even though EDs are structurally similar.
Jung
Ki Kyung
KK
Department of Pharmacology, Biochemical Pharmacology Team, National Institute of Toxicological Research, Seoul 122-704, Korea.
Kim
So Young
SY
Kim
Tae Gyun
TG
Kang
Ju Hye
JH
Kang
Seog Youn
SY
Cho
Jae Youl
JY
Kim
Seung Hee
SH
D000818:Animals; D001559:Benzhydryl Compounds; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity; D052244:Endocrine Disruptors / Q000633:toxicity*; D010636:Phenols / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D011388:Prolactin / Q000096:biosynthesis; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000187:drug effects* / Q000502:physiology; D014284:Triiodothyronine / Q000494:pharmacology; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D020111:Chlorodiphenyl (54% Chlorine); D052244:Endocrine Disruptors; D010636:Phenols; D000072317:Polychlorinated Dibenzodioxins; D011388:Prolactin; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; C006780:bisphenol A; D000098826:Bisphenol A Compounds