Effects of Propylthiouracil and Thiouracil on the Metabolism of Thyroxine and Several of Its Derivatives by Rat Kidney Slicesin Vitro1

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Abstract
The metabolism of thyroxine (T4), 3,5,3′-L-triiodothyronine (T3), tetraiodothyroacetic acid (TA4) and triiodothyroacetic acid (TA3) by rat kidney slices in vitro has been studied to determine the effects of thiouracil (TU) added in vitro and of propylthiouracil (PTU) administered in vivo. These agents decreased the deiodination of T4 and increased the generation of conjugates, without altering the tissue oxygen consumption. Perchlorate and methimazole, comparably administered, were without effect. TU and PTU induced alterations in the metabolism of TA4 and T3 similar to those which occurred in the case of T4. However, the effects were less consistent with T3 than with T4. The results obtained with TA3 were highly variable, significant alterations of in vitro metabolism being obtained in less than half the experiments. In separate experiments, the prevention of PTU-induced goiters by varying doses of T4 was studied in order to correlate the effects upon tissue QO2, T4 deiodination and serum PBI. In confirmation of the results obtained by other workers, doses of T4 adequate to restore PBI to normal failed to prevent goiter completely, while goiter-preventing doses were associated with abnormally high PBI’s. Tissue respiration, as assessed in slices of renal cortex, demonstrated a close inverse correlation with thyroid size. The percentile deiodination of T4 was inhibited in all groups given PTU, regardless of whether or not T4 was also administered. The findings are discussed in the light of the hypothesis that hormonal deiodination and hormonal action are closely linked.