Effects of methylmercaptoimidazole (MMI), propylthiouracil (PTU), potassium perchlorate (KClO4) and potassium iodide (KI) on the serum concentrations of thyrotrophin (TSH) and thyroid hormones in the rat.
Male Sprague-Dawley rats were given graded doses of methylmercaptoimidazole (MMI), propylthiouracil (PTU), KClO4 or KI in drinking water for 4 days, or the lowest effective dose of each drug for various times. The rats were sacrificed at 1--2 p.m. and serum T3, T4 and TSH concentrations were measured by radioimmunoassays. It was found that administration of 5 mg/l of MMI, 10 mg/l of PTU and 100 mg/l of KClO4 for 4--14 days induced a transient rise in serum TSH and a fall in serum T3 or T4 or in both. The effects of KI were not consistent. In another series of experiments, PTU (10 mg/l) was given in drinking water for 4 days, and then graded doses of T3 or T4 were given iv, or 100 ng of TRH was injected into a tail vein, or the animals were exposed to 4 degrees C for 30 min. The initial high TSH levels were further increased by TRH and cold and decreased by T3 and T4. The PTU-treated animals had goitres after 4 days. We infer that low doses, that is to say 10--100 times lower than previously described, of antithyroid drugs induce a hypothyroidism characterized by an increased TSH level and a decreased serum T3 or T4 level or both. A 4 days' treatment with PTU (40 mg/l in tap water) is a suitable tool for studying the effect of various conditions on TSH secretion.
D000818:Animals; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology*; D011193:Potassium Iodide / Q000008:administration & dosage / Q000494:pharmacology*; D011441:Propylthiouracil / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects; D013972:Thyrotropin / Q000097:blood*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D013974:Thyroxine / Q000097:blood* / Q000494:pharmacology; D014284:Triiodothyronine / Q000097:blood* / Q000494:pharmacology
D007093:Imidazoles; D014284:Triiodothyronine; D011193:Potassium Iodide; D013973:Thyrotropin-Releasing Hormone; D011441:Propylthiouracil; D013972:Thyrotropin; D013974:Thyroxine; D011188:Potassium