The effect of propylthiouracil on the intrathyroid metabolism of iodine in rats.

It has long been known that treatment with propylthiouracil and other antithyroid drugs inhibits organic binding of iodine and leads to a reduction in total iodine in the thyroid (1). The work of Franklin et al. (2-4) showed that these agents also prevent incorporation of radioiodine into organic compounds by thyroid slices in Z.&O. Pitt-Rivers (5), finding that acetyldiiodotyrosine did not form acetylthyroxine when incubated with these compounds, suggested that they may act by inhibiting coupling of diiodotyrosines to form thyroxine in vivo. However, Slingerland (6) was unable to obtain evidence in support of this possibility. Recent investigations have suggested that although propylthiouracil blocks the iodination of tyrosyl groups in thyroglobulin, it inhibits the formation of diiodotyrosine more strongly than the formation of monoiodotyrosine. Slingerland et al. (7) felt that this block favored the synthesis of triiodothyronine over that of thyroxine, whereas Richards and Ingbar (8) found no triiodothyronine and a reduced quantity of thyroxine in the glands of rats treated with small amounts of propylthiouracil. All of the studies on the effect of propylthiouracil on the intrathyroid metabolism of radioiodine have been conducted by administration of radioiodine after treatment with graded doses of the drug. In the studies to be described we thought it might be informative to “label” the thyroids of animals before drug treatment and to follow subsequently the radioactivity in the several iodine-containing compounds in the glands after instituting antithyroid treatment.