ToxSci Advance Access originally published online on July 13, 2006
Toxicological Sciences 2006 93(2):278-285; doi:10.1093/toxsci/kfl063
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The Effects of Methimazole on Development of the Fathead Minnow, Pimephales promelas, from Embryo to Adult
* School of Biosciences, Hatherly Laboratories, Prince of Wales Road, University of Exeter, Exeter EX4 4PS, United Kingdom; AstraZeneca, Global Safety, Health and Environment, Brixham Environmental Laboratory, Freshwater Quarry, Brixham, Devon TQ5 8BA, United Kingdom; and Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH, United Kingdom
Received April 26, 2006; accepted June 26, 2006
The importance of thyroid hormones in regulating early developmental processes of many amphibian and fish species is well known, but the impacts of exposure to disrupters of thyroid homeostasis during the embryo-larval-juvenile transitions are unclear. To investigate these impacts, fathead minnows, Pimephales promelas, were exposed to a model thyroid axis disrupter, methimazole, an inhibitor of thyroid hormone synthesis, at control (0), 32, 100, and 320 µg/l, starting at <24-h postfertilization, for 28, 56, and 83/84 days postfertilization (dpf). Thyroid disruption was evident at 28 dpf, when survival was significantly reduced by 32 or 100 µg/l methimazole concomitant with a reduced thyroxine (T4) content. However, the T3 content of these fish was similar to that of control fish, and body mass was unaffected (as in all groups), suggesting compensatory mechanisms overcame reduced T4 synthesis. At the highest concentration of methimazole (320 µg/l), activation of feedback mechanisms on the hypothalamic-pituitary-thyroid axis was suggested by the normal T4 content after 28 dpf exposure to methimazole, although triiodothyronine (T3) content of these fish was significantly reduced. The generally less pronounced disruption of thyroid hormone homeostasis after 56 days exposure to methimazole also suggests compensatory mechanisms in juvenile/adult fish that may regulate T4 content, despite exposure to methimazole at 32 or 100 µg/l (in fish held in 320 µg/l methimazole, the T4 content was significantly higher than in controls). Whole body T3 content at 56 dpf was significantly depressed only in fish held in 100 µg/l methimazole. By 83/84 dpf, length, body mass, and thyroid hormone concentrations were similar in all experimental groups and controls, indicating that adult fish may achieve regulation of their thyroid axis despite prolonged exposures to thyroid disruptors throughout early development.
Key Words: thyroid; thyroxine; triiodothyronine; development; methimazole; fathead minnow.