1999 Fiscal Year Final Research Report Summary
STUDIES ON THE EXPRESSION OF THYROTROPIN RECEPTORS IN THYMUS.
| Project/Area Number |
09671024
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Gunma University, School of Medicine |
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Principal Investigator |
MURAKAMI Masami GUNMA UNIVERSITY SCHOOL OF MEDICINE, FIRST DEPARTMENT OF INTERNAL MEDICINE, INSTRUCTOR, 医学部, 助手 (30241871)
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| Project Period (FY) |
1997 – 1999
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| Keywords | thyroid / thymus / thyrotropin receptor / iodothyronine deiodinase / thyroid hormone / Graves disease / apoptosis / antithyroid drug |
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| Research Abstract |
We have reported that thymic hyperplasia is associated with Graves disease that results from the development of antibodies for thyrotropin (TSH) receptors and demonstrated that TSH receptors are expressed in human thymus. Thymic TSH receptors may be involved in the initiation or perpetuation of the autoimmune response, and in the selection of the T cell repertoire that may contribute to the development of autoreactive T cells in Graves disease, as suggested for thymic acetylcholine receptors in myasthenia gravis.
TSH receptor mRNA was expressed in thymic tissue of 5, 10 and 20-day-old and adult rat. TSH receptor mRNA was expressed in cultured rat thymic epithelial cells and TSH stimulated cAMP production in cultured rat thymic epithelial cells in a dose dependent manner, suggesting the expression of functional TSH receptors in thymic epithelial cells. Expression of TSH receptors in rat thymic epithelial cells suggests that thymic TSH receptors may be involved in the initiation or perpet
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uation of the autoimmune response, and in the selection of the T cell repertoire that may contribute to the development of autoreactive T cells in Graves disease. Thymic weight decreased in both thyroidectomized and methimazole (MMI) treated rats in the similar manner. The number of apoptotic cells in thymus increased in thyroidectomized and MMI treated rats. These results suggest that the reduction in thymic size after antithyroid drug treatment observed in patients with Graves' disease may be related, at least in part, to the decrease in circulating thyroid hormone levels.
TィイD24ィエD2, which is the major secretory product of thyroid gland, needs to be converted to TィイD23ィエD2 to exert its biological activity by iodothyronine deiodinases. Type II iodothyronine deiodinase (DII) has a critical role to provide local TィイD23ィエD2. We have demonstrated DII expression in human thymic tissue, suggesting the physiological role of DII in thymus for the effect of thyroid hormones. We have successfully isolated human DII gene to study the regulation mechanisms of DII expression. We have characterized its chromosomal localization and analyzed its promoter region. Less
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