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A thyroid hormone antagonist has not been previously described. A number of thyroid hormone analogues have been shown to compete with [125I]triiodothyronine ([125I]T3) for binding to the intranuclear thyroid hormone receptor and to have agonist activity proportional to their affinities for the receptors. We report that the benzofuran amiodarone acts as a competitive antagonist to thyroid hormone action as defined by its dose-dependent ability to (a) bind to the thyroid hormone receptor and (b) inhibit T3-induced increases in growth hormone mRNA levels in a cultured rat pituitary cell line, GC cells. Like T3 itself, amiodarone also decreases transport of [125I]T3 across GC cell membranes. An analysis of the amiodarone structure suggests that this compound has certain similarities to T3. These findings hold promise for the development of other thyroid hormone antagonists for clinical use and for understanding thyroid hormone action.

Antagonism of thyroid hormone action by amiodarone in rat pituitary tumor cells.