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PubMed1976

Inhibitory effect of large doses of propylthiouracil and methimazole on an increase of thyroid radioiodine release in response to thyrotropin.

Thyroidal radioiodine release increased shortly after a single injection of small doses of PTU, while moderate doses of MMI produced a similar increase of thyroidal radioiodine release with a latency of 7-9 hr. Large doses of PTU and MMI failed to augment thyroidal radioiodine release for at least 29 to 34 hr after the initial administration of goitrogens, although plasma TSH increased significantly because of goitrogen administration. An increase of thyroid hormone release in response to exogenous TSH was depressed by PTU and MMI in rats and mice treated with T4. Since this depression of TSH action only continued for a short period in spite of continuous administration of goitrogens, and since final thyroidal radioiodine release rate was similar to that produced by small doses of PTU, the effects mentioned were not simply due to general toxic action of goitrogens. It is suggested that large doses of PTU and MMI not only block thyroid hormone synthesis but also interfere with the action of TSH on thyroid hormone secretion.

Animals↗
PubMed1976

Increase of serum free thyroxine after propylthiouracil in vitro or its peroral administration to rats.

After the addition of 6-propyl-2-thiouracil (PTU) (2.4 mg/ml) in vitro to the normal human serum a two fold increase of dialyzable free thyroxine fraction (%FT4) was found. The addition of the same PTU dose to the serum of intact Wistar rats caused up to 4 fold increase of this fraction. After the addition of increasing doses of PTU (40--400 ng/ml) a linear increase of FT4 was found in human serum, while in rat serum a nonlinear dose-response relationship was observed. After a single peroral administration of PTU to rats (42 mg PTU per animal) the serum PTU level reached the maximum (55 ng PTU/ml) after one hour and then decreased very slowly. The free thyroxine fraction also increased up to 150% of control value, but this maximum increase was observed one hour to later then the maximum PTU level. Then the values of %FT4 rapidly decreased to the initial value. Such effect of PTU in vivo was about twofold greater than that obtained in the rat serum in vitro under the same actual PTU level. The results were compared with similar effect of thiocyanate reported previously and it was shown that the effect of PTU both in vitro and in vivo is greater than that of equimolar levels of thiocyanate.

Administration, Oral↗