Selective inhibition of the secretion of triiodothyronines from the perfused canine thyroid by propylthiouracil

In order to assess a possible influence on the relative proportions of T4, T3, and rT3 in thyroid effluent, the thyroid-blocking agents, propylthiouracil (PTU) and methylmercaptoimidazol (MMI), were administered to perfused canine thyroids. The dog has two distinct thyroid lobes which were both perfused independently, one acting as a control for the other. T4, T3, and rT3 in thyroid effluents and thyroid hydrolysates were measured radioimmunologically. During control perfusion the T4:T3 and T4:rT3 ratios in thyroid effluent were considerably lower than in thyroid hydrolysates [t4:t3 (wt/wt), 6.1 +/- 2.0 vs. 12.8 +/- 4.4; T4:rT3, 23.0 +/- 5.9 vs. 69.7 +/- 29.1; mean +/- SD; n = 8; P less than 0.001], i.e. T3 and rT3 were secreted preferentially to T4. Infusion of PTU (1 mmol/liter) induced a gradual increase in both the T4:T3 and T4:rT3 ratios in thyroid effluent. The variation in the T4:rT3 ratio appeared somewhat earlier than that in the T4:T3 ratio. Both ratios eventually approached the ratios in thyroid hydrolysates. The change in ratios was caused by a PTU-induced decrease in the release of T3 and rT3 while the release of T4 was practically unaffected. In contradistinction, infusion of MMI did not affect the T4:T3 or T4:rT3 ratios in thyroid effluent. As PTU but not MMI inhibits T4 deiodination in peripheral tissues, the results of the present study suggest that part of the T3 and rT3 secreted from the thyroid stems from T4 deiodinated during the secretion by a mechanism similar to the T4-deiodinating processes in peripheral tissues.