This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by NAGASAKA, A. Articles by HIDAKA, H. Search for Related Content PubMed PubMed Citation Articles by NAGASAKA, A. Articles by HIDAKA, H.

Effect of Antithyroid Agents 6-Propyl-2-Thiouracil and l-Methyl-2-Mercaptoimidazole on Human Thyroid Iodide Peroxidase

First Department of Internal Medicine, Faculty of Medicine University of Nagoya, Nagoya
^* Department of Biochemistry, Institute for Developmental Research Aichi Prefecture Colony, Kasugai, Aichi, 480-03, Japan

^* Reprints should be requested from H. Hidaka, M.D., Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606, Japan.

The mechanism of inhibition of human thyroid iodide peroxidase (TPO) by 6-propyl-2-thiouracil (PTU) and l-methyl-2-mercaptoimidazole (MMI) used in the therapy of hyperthyroid patients was studied in vitro. The inhibition of TPO by MMI was not restored either by dialysis or by dilution, but the inhibition by PTU was restored by both treatments. PTU interacted directly with the product of TPO action (oxidized iodide) in the reaction mixture without significantly affecting TPO activity. MMI interacted directly with TPO and inhibited enzyme activity, rather than interacting with the product (oxidized iodide). The inhibition was irreversible with MMI, but reversible with PTU. The concentrations of PTU and MMI producing 50% inhibition of TPO were 2 x 10^–6M and 8 x 10^–7M, respectively. 2-Mercaptoimidazole inhibited TPO reversibly but 1-methylimidazole and imidazole did not. Both the methyl and mercaptoresidues in MMI moiety are thought to be essential to its irreversible inhibition of TPO.

The in vivo effect of MMI and PTU on TPO activity was also studied. TPO activities in the thyroid homogenate of rats to which MMI (2 mg per rat) or PTU (10 mg per rat) had been administered intraperitoneally were determined before and after dialysis against buffer. TPO activity in the PTUtreated thyroid homogenate was significantly lower than that in the control before dialysis, but the activity was restored to the control value after dialysis. On the contrary, TPO activity in the MMI treated thyroid homogenate was significantly lower than that in the control and was not affected by dialysis.

These data may explain why MMI is a more potent inhibitor of iodination than PTU and may fit the clinical results observed when hyperthyroid patients are treated with these agents.

Supported by Imanaga and Takeda Science Foundations.

These data were presented before the 47th Congress of Japan Endocrine Society, April, 1974 Folia Endocrinol Jap (Abstract) 50: 122, 1974.

Received May 19, 1975.

This article has been cited by other articles:

				M. Qatanani, J. Zhang, and D. D. Moore Role of the Constitutive Androstane Receptor in Xenobiotic-Induced Thyroid Hormone Metabolism Endocrinology, March 1, 2005; 146(3): 995 - 1002. [Abstract] [Full Text] [PDF]

				D. C. Norford, D. J. Meuten, J. M. Cullen, and J. J. Collins Pituitary and Thyroid Gland Lesions Induced by 2-Mercaptobenzimidazole (2-MBI) Inhalation in Male Fischer-344 Rats Toxicol Pathol, September 1, 1993; 21(5): 456 - 464. [Abstract] [PDF]