The goitrogenic efficiency of thioamides in a marine teleost, sea bream (Sparus auratus)

Abstract

Studies on the role of thyroid hormones (THs) in teleost fish physiology have deployed the synthetic goitrogens, methimazol (MMI), propilthiouracil (PTU) and thiourea (TU) that are used to treat human hyperthyroidism. However, the action of the goitrogens, MMI, PTU and TU at different levels of the hypothalamic–pituitary–thyroid (HPT) axis in teleosts is largely unknown. The central importance of the hypothalamus and pituitary in a number of endocrine regulated systems and the cross-talk that occurs between different endocrine axes makes it pertinent to characterize the effects of MMI, PTU and TU, on several endpoints of the thyroid system. The marine teleost, sea bream (Sparus auratus) was exposed to MMI, PTU and TU (1 mg/kg wet weight per day), via the diet for 21 days. Radioimmunoassays (RIA) of plasma THs and ELISA of the TH carrier transthyretin (TTR) revealed that MMI was the only chemical that significantly reduced plasma TH levels (p < 0.05), although both MMI and PTU significantly (p < 0.05) reduced plasma levels of circulating TTR (p < 0.05). Histological analysis of the thyroid tissue revealed modifications in thyrocyte activity that explain the reduced circulating levels of THs. MMI also significantly (p < 0.05) up-regulated transcript abundance of liver deiodinase 1 and 2 while significantly (p < 0.05) decreasing TRb expression in the pituitary, all hallmarks of HPT axis action of goitrogens in vertebrates. The results indicate that in the sea bream MMI is the most effective goitrogen followed by PTU and that TU (1 mg/kg wet weight for 21 days) failed to have a goitrogenic effect. The study highlights the non-uniform effect of goitrogens on the thyroid axis of sea bream and provides the basis for future studies of thyroid disrupting pollutants.This work was funded by the Portuguese Science Foundation through Grants SFRH/BPD/66808/2009 to MA Campinho and SFRH/BPD/25247/2005 to PIS Pinto. We acknowledge Alejandro Pinzon for his contribution in preliminary studies