Increased Secretion of Thyrotrophic Hormone in Rats with a Depressed Peripheral Deiodination of Thyroid Hormone and a Normal or High Plasma PBI

The administration of propylthiouracil to intact rats results in an increased TSH release by the pituitary within the first 24 hr of treatment. This conclusion is supported by the results of thyroidal histology, I131 secretion rates, plasma and pituitary TSH assays and pituitary cytology. During this early phase of treatment the plasma PBI1 is normal, but the peripheral deiodination of thyroid hormone is depressed. The administration of L-thyroxine in high doses avoids this early response to PTU. The administration of PTU to thyroidectomized rats on a physiologic L-thyroxine maintenance dose results in an increased secretion of TSH by the pituitary. An increased plasma PBI, unaltered concentration of iodine-containing compounds in most peripheral tissues, and a sharply depressed peripheral deiodination of thyroxine are concomitant findings. Maintenance of the thyroidectomized rats on a high dose of Lthyroxine avoids an increase in TSH secretion during PTU administration. The results are discussed in terms of thyroid-pituitary interrelationships and of the mechanism of PTU-induced goitrogenesis. The present data support the idea that the regulator (s) of the negative feedback system which are responsible for the triggering of TSH secretion appear to be sensitive to intracellular factors related to the deiodination and metabolic effectiveness of the thyroid hormone rather than to its concentration in the blood.