An Essential Role of Thyroxine and Triiodothyronine Balance in Establishing Normal Pituitary-Thyroid Feedback Control in Goitrogen-Treated Rats

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Abstract
Rats were fed propylthiouracil (0.05%), methi-mazole (0.05%), or sulfaeuanidine (1%) and injected with graded doses of T4 (0.5-3.0 [mu]g) daily for 2 weeks. In spite of the high serum PBI with doses of 1.0 and 1.5 [mu]g of T4, goiter was still observed in animals fed propylthiouracil. Goiter was prevented only when the PBI was increased to 2.2 times that of the control level by giving 2.0 [mu]g of T4. Similar effects were found with methimazole and sulfaguanidine. In animals which were thyroidectomized and given T4, methimazole slightly elevated the serum PBI and reduced the urinary excretion of radioiodine after a single injection of labeled T4. However, since sulfaguanidine was without effect in these respects, the developme nt of goiter in the presence of a high serum PBI cannot be explained by assuming that all 3 goitrogens interfered with the deiodination of T4. On the other hand, goiter was prevented in propylthiouracil-fed animals by doses of thyroid powder which resulted in a serum PBI lower than normal. Furthermore, goiter prevention in methimazole-fed animals was achieved by administering a mixture of T3 (0.1 [mu]g) and T4 (1.0 [mu]g) which produced a normal serum PBI and thyrotropin level. Since normally T3 plays an important physiologic role, goiter could not be prevented without giving a dose of T4 that would elevate the serum PBI to compensate for the activity of T3. The existence of a homeostatic relation between the level of serum PBI and thyrotropin secretion by the anterior pituitary can be shown in goitrogen-treated animals only when an appropriate mixture of T3 and T4 is administered.