STUDIES ON THE PATHOGENESIS OF GRAVES' DISEASE
| Project/Area Number |
60480517
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Yamanashi Medical College |
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Principal Investigator |
ONAYA Toshimasa The Third Department of Internal Medicine, Yamanashi Medical College. Professor., 医学部, 教授 (40020812)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Graves' disease / Hyperthyroidism / Thyroid Hormone / Prostacyclin / TSH Receptor Antibody / Human Thyroid Stimulator / TRAb / トロンボキサン |
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| Research Abstract |
1. THE STIMULATORY EFFECT OF THYROID HORMONE ON <PGI_2> PRODUCTION: Plasma <PGI_2> levels were significantly increased in hyperthyroid rats, but reduced in hypothyroid rats treated with methimazole. The increased plasma <PGI_2> levels and reduced thromboxane <A_2> levels in untreated hyperthyroid patients with Graves' disease were normalized after antithyroid drug therapy. Furthermore, in in vitro experiment, <PGI_2> production by cultured vascular smooth muscle cells was significantly stimulated by the addition of triiodothyronine to the medium. Therefore, the data suggest that there exists an vicious circle in the pathophysiology of Graves' disease (TSH-receptor antibody---stimulation of thyroid hormone secretion---increased thyroid hormone levels---increased <PGI_2> production---stimulation of thyroid hormone secretion).
2. THE MECHANISM OF ACTION OF THYROID STIMULATOR AND <CA^(2+)> :
(1) Phorbol esters, protein kinase C activator, stimulated protein phosphorylation and thyroid hormone secretion in vitro.
(2) Calmodulin antagonists markedly inhibited TSH-stimulated thyroid hormone secretion in vitro.
(3) Calpains, <Ca^(2+)> -dependent proteases, exist in the thyroid cytosol and can hydrolyze thyroglobulin.
Therefore, in many aspects, <Ca^(2+)> plays an important role in thyroid activation by the thyroid stimulators.
3. PARVALBUMIN AND THYROID FUNCTION:
Parvalbumin, an <Ca^(2+)> -binding protein and rich in type <II> muscular fibers, was increased in hyperthyroid rats and markedly reduced in hypothyroid rats. Parvalbumin may be related to the pathophysiology of muscular atrophy observed in hyperthyroid patients with Graves' disease and also in hypothyroid patients.
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Report
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Research Products
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