1988 Fiscal Year Final Research Report Summary
Studies on pathogenesis of primary hypothyroidism
| Project/Area Number |
62570510
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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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 | Kyoto University |
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Principal Investigator |
KASAGI Kanji Department of Medicine, 医学部, 講師 (20115819)
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| Co-Investigator(Kenkyū-buntansha) |
KONISHI Junji Department of Medicine, 医学部, 教授 (70026970)
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| Project Period (FY) |
1987 – 1988
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| Keywords | ^<125>l uptake / cAMP / primaty hypothyroidism / Hashimoto's thyroidits / TSH receptor / thyroid stimulating immunoglobulins(TSI) / TSH刺激抑制抗体 / TSI / TBII |
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| Research Abstract |
We studied the effects of crude immunoglobulin(lg) fractions of serum from patients with goitrous and atrophic autoimmune thyroiditis on TSH-, thyroid-stimulating immuno-globulin(TSI)-, forsholin, and dibutyryl cAMP-stimulated ^<125>l uptake by FRTL-5 thyroid cells. TSH-stimulated ^<125>l uptake was inhibited by the lg fractions from 15 patients with atrophic thyroiditis who had serum TSH-binding inhibitor lg(TBII), 10(62.5 %) of 16 TBII-negative patients with atrophic thyroiditis, 7(43.8 %) of 16 hypothyroid patients with goitrous thyroiditis who had no TBII activity, and only 2(15.4 %) of 13euthyroid patients with goitrous thyroiditis who were negative for TBII. The mean inhibition of TSH-stimulated ^<125>l uptake produced by the crude lgs from the former 3 groups of hypothyroid patients was statistically significant(O<0.001, P<0.001, and p<0.01, respectively) and correlated closely with the ability of the lg to inhibit TSI-stimulated ^<125>l uptake (r=0.882) and TSH-stimulated cAMP accumulation(r=0.929). The inhibition of TSH- or TSI- stimulated ^<125>l uptake by lg samples containing TBII correlated significantly with the TBII activities. On the other hand, in the presence of lgs from TBII-negative hypothyroid patients, the inhibition of TSH-stimulated ^<125>l uptake correlated significantly with that of forskolin-stimulated ^<125>l upatke(r=0.685). Although 6(12.8 %) of 47 lg samples from hypothyroid patients inhibited dibutyryl cAMP-stimulated ^<125>l uptake, the activities were marginal. These findings suggest that at least 2 types of antibodies are involved in the inhibition of TSH- or TSI-stimulated ^<125>l uptake: 1 being a competitive inhibitor of TSH-binding to its receptors, and another exerting influence on a step sdubsequent to TSH or TSL binding, presumably through adenylate cyclase inhibition.
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[Publications] Tokuda,Y,;Kasagi,K,;Iida,Y,;Hatabu,H,;Misaki,T,;Arai,K,;Endo,K,;Konishi,J.: J.Clin.Endocrinol.Metab.67. 251-258 (1988)
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