The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development

We investigated whether exposure to environmentally relevant concentrations of the bactericidal agent, triclosan, induces changes in the thyroid hormone-mediated process of metamorphosis of the North American bullfrog, Rana catesbeiana and alters the expression profile of thyroid hormone receptor (TR) alpha and beta, basic transcription element binding protein (BTEB) and proliferating nuclear cell antigen (PCNA) gene transcripts. Premetamorphic tadpoles were immersed in environmentally relevant concentrations of triclosan and injected with 1 x 10(-11) mol/g body weight 3,5,3'-triiodothyronine (T-3) or vehicle control. Morphometric measurements and steady-state mRNA levels obtained by quantitative polymerase chain reaction were determined. mRNA abundance was also examined in Xenopus laevis XTC-2 cells treated with triclosan and/or 10nM T-3. Tadpoles pretreated with triclosan concentrations as low as 0.15 +/- 0.03 mu g/L for 4 days showed increased hindlimb development and a decrease in total body weight following T-3 administration. Triclosan exposure also resulted in decreased T-3-mediated TR beta mRNA expression in the tadpole tail fin and increased levels of PCNA transcript in the brain within 48 h of T-3 treatment whereas TR alpha and BTEB were unaffected. Triclosan alone altered thyroid hormone receptor alpha transcript levels in the brain of premetamorphic tadpoles and induced a transient weight loss. In XTC-2 cells, exposure to T-3 plus nominal concentrations of triclosan as low as 0.03 mu g/L for 24 h resulted in altered thyroid hormone receptor mRNA expression. Exposure to low levels of triclosan disrupts thyroid hormone-associated gene expression and can alter the rate of thyroid hormone-mediated postembryonic anuran development. (c) 2006 Elsevier B.V All rights reserved.