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Antithyroid Drugs Inactivate TSH Binding to the TSH Receptor by their Reducing Action

[ Vol. 18 , Issue. 5 ]


Yukio Ochi*, Takashi Hachiya, Yukiko Koyama, Nobutoshi Fukuhori and Noriyuki Ashida   Pages 508 - 512 ( 5 )


Backgroud and Objective: Antithyroid drugs (ATDs) [methylmercaptoimidazole (MMI) and propylthiouracil (PTU) ] are used to treat hyperthyroidism in Graves’ disease. The effect of ATDs and reducing agents (mercaptoethanol, dithiothreitol and cysteine) on bovine (b) TSH binding to human (h) and porcine (p) TSH receptor (R) was examined.

Methods and Results: (1) ATDs was pre-incubated with hTSHR coated tube for 1- 4 h, washed free of ATDs, and then 125I-bTSH binding to hTSHR after 1 h incubation was examined. MMI (10–40 mM) decreased 125I-bTSH binding in a dose-dependent manner and binding decreased proportionally as preincubation time increased from 1 to 4 h. PTU (10mM) slightly decreased binding, When reducing agents were pre-incubated with hTSHR for 2 h, 125I-bTSH binding similarly decreased. (2) Porcine thyroid membrane was pre-incubated with both agents for 2 h. Then, the washed or unwashed membrane was incubated with 125I-bTSH for 1 h. 125I-bTSH binding in both methods decreased. (3) When the effect of ATDs or reducing agents on the biological activity of 125I-bTSH and thyroid stimulating antibody (TSAb) was examined after gel-filtration of 125I-bTSH- and TSAb- treated with both reagents for 1 h, no inactivation was observed. (4) ATDs showed similar reducing action as reducing agents because iodine (I+) was reduced to I- by ATDs.

Conclusion: ATDs inactivate the TSH-binding site of TSHR by reduction, although ATDs do not inactivate bTSH and TSAb activity. This suggests that TSAb would not stimulate the thyroid due to the inactivation of the TSHR when ATDs are administered to patients with Graves’ disease.


Antithyroid drug, TSH receptor, reducing agent, Graves` disease, thyroid stimulating antibody, hyperthyroidism.


Research Institute for Production Development, Kyoto 606-0805, Midorigaoka Hospital, Takatsuki, Osaka 569-1121, Radioisotope Research Center, Shiga University of Medical Science, Otsu, Shiga 520-2192, Radioisotope Research Center, Shiga University of Medical Science, Otsu, Shiga 520-2192, Yamasa Ltd, Choshi, Chiba 288-0056

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