title: The effects of methimazole on development of the fathead minnow, Pimephales promelas, from embryo to adult.
abstract: 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 mug/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 mug/l methimazole concomitant with a reduced thyroxine (T(4)) content. However, the T(3) 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 T(4) synthesis. At the highest concentration of methimazole (320 mug/l), activation of feedback mechanisms on the hypothalamic-pituitary-thyroid axis was suggested by the normal T(4) content after 28 dpf exposure to methimazole, although triiodothyronine (T(3)) 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 T(4) content, despite exposure to methimazole at 32 or 100 mug/l (in fish held in 320 mug/l methimazole, the T(4) content was significantly higher than in controls). Whole body T(3) content at 56 dpf was significantly depressed only in fish held in 100 mug/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.
authors.affiliation: School of Biosciences, Hatherly Laboratories, Prince of Wales Road, University of Exeter, Exeter EX4 4PS, United Kingdom. helen.jordinson@environment-agency.gov.uk
authors.forename: Helen M
authors.initials: HM
authors.lastname: Crane
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Pickford
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hutchinson
authors.forename: J Anne
authors.initials: JA
authors.lastname: Brown
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000633:toxicity*; D003530:Cyprinidae / Q000196:embryology*; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000502:physiology; D005260:Female; D008297:Male; D008713:Methimazole / Q000633:toxicity*; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: D013956:Antithyroid Agents; D013963:Thyroid Hormones; D008713:Methimazole