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Early Temporal Effects of Three Thyroid Hormone Synthesis Inhibitors in Xenopus laevis
Citation:
TIETGE, J. E., B. C. BUTTERWORTH, J. HASELMAN, G. W. HOLCOMBE, M. HORNUNG, J. J. KORTE, P. A. KOSIAN, S. J. DEGITZ, AND M. WOLFE. Early Temporal Effects of Three Thyroid Hormone Synthesis Inhibitors in Xenopus laevis. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, 98(1):44-50, (2010).
Impact/Purpose:
Changes in thyroidal histology and cell number represent compensatory effects modulated by circulating TSH. These observations set the stage for further investigations into the development of short term methods to evaluate chemicals which disrupt normal TH homeostasis.
Description:
Thyroid axis disruption is an important consideration when evaluating the risks associated with chemicals. Bioassay methods that include thyroid-related endpoints have been developed in a variety of species, including amphibians, whose metamorphic development is thyroid hormone (TH)-dependent. Inhibition of TH synthesis in these species leads to developmental delay and assays designed to capture these effects take several weeks to complete. In an effort to develop a shorter term approach, the early responses of various endpoints were evaluated in Xenopus laevis throughout eight days of exposure to three TH synthesis inhibitors: methimazole (100 mg/L), 6-propylthiouracil (20 mg/L), and perchlorate (4 mg/L). Endpoints included thyroid gland histology and cell numbers, circulating TH concentrations, and thyroidal TH and associated iodo-compounds. Thyroidal T4 and DIT were reduced on day 2 by all three chemicals, representing the earliest indication of TH synthesis inhibition. Thyroidal MIT was reduced by methimazole and perchlorate by days 2 and 4, respectively, but not by PTU. Histological effects were apparent on day 4 and became more exaggerated through day 8. However, reductions in circulating T4 and increases in thyroid gland cell numbers were not apparent until day 6. Changes in thyroidal MIT, DIT, and T4, as well as circulating T4 are indicative of inhibitory effects on TH synthesis. Changes in thyroidal histology and cell number represent compensatory effects modulated by circulating TSH. These observations set the stage for further investigations into the development of short term methods to evaluate chemicals which disrupt normal TH homeostasis.