The efficacy of iodide and thyroxine in ameliorating the several deficiencies occasioned by thyroidectomy in male and female rats was compared in order to obtain indirect evidence for extrathyroidal thyroxine formation. More direct refutation of the opposing concept that iodide simulates the action of thyroxine was also sought in experiments with propylthiouracil (PTU) and tribromothyronine. In all indices of thyroxine action examined in thyroidectomized rats, namely, growth, metabolic rate, heart rate, and pituitary, adrenal and reproductive function, the restorative or maintenance activities of large quantities of iodide were identical with those of minute quantities of thyroxine. Effective doses of iodide presumably resulted in the formation of thyroxine in quantities equivalent to the daily injection of 0.25-0.5 ng. PTU abolished most of the growth response to iodide, while not interfering with the action of thyroxine, which pro
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