Antithyroid effects of propylthiouracil and sulfamonomethoxine in rats and monkeys.
Experiments were performed to investigate the species difference in antithyroid effects of propylthiouracil (PTU) and sulfamonomethoxine (SMM). Sprague-Dawley rats were administered 30 mg/kg of PTU, or 30 or 270 mg/kg of SMM orally for 5 weeks, while squirrel monkeys received 30 mg/kg of PTU or 270 mg/kg of SMM. In rats receiving 30 mg/kg of PTU, a decrease of both serum 3,5,3'-triiodothyronine and thyroxine concentrations and of 131I incorporation into the thyroid hormone precursors was observed, together with elevation of serum thyroid-stimulating hormone concentration, an increase in thyroid weight, and hyperplasia of the follicular epithelium of the thyroid gland. Similar changes were seen in rats receiving 270 mg/kg of SMM; however, the antithyroid effects of SMM were less severe than those of PTU. No change was produced in monkey thyroids by 5-week treatments with 30 mg/kg of PTU or with 270 mg/kg of SMM. The molar concentration of PTU required for the in vitro inhibition of thyroid peroxidase was markedly lower in rats than in monkeys. SMM showed a similar species difference in the inhibition of thyroid peroxidase in vitro, but the enzyme inhibition of SMM was weaker than that of PTU. These findings suggest that rats were more sensitive to the antithyroid effects of PTU and SMM than monkeys, and that inhibition of thyroid peroxidase may play an important role in species difference in the antithyroid effects of the two drugs.
S
S
Takayama
K
K
Aihara
T
T
Onodera
T
T
Akimoto
D000818:Animals; D013956:Antithyroid Agents; D066298:In Vitro Techniques; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors; D007455:Iodine / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011441:Propylthiouracil / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012453:Saimiri; D013045:Species Specificity; D013422:Sulfamonomethoxine / Q000494:pharmacology*; D013424:Sulfanilamides / Q000494:pharmacology*; D013961:Thyroid Gland / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D013956:Antithyroid Agents; D013424:Sulfanilamides; D014284:Triiodothyronine; D011441:Propylthiouracil; D013972:Thyrotropin; D007455:Iodine; D007453:Iodide Peroxidase; D013974:Thyroxine; D013422:Sulfamonomethoxine