Studies on the metabolism and action of thyroid hormone with emphasis on its role in neurotransmission

研究甲状腺激素的代谢和作用，重点关注其在神经传递中的作用

• 批准号: 03671147
• 负责人: TANAKA Kiyoshi
• 金额: $ 1.28万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03671147/
• 关键词: Thyroid Hormone; Metabolism; Brain; Pituitary; Pineal; deiodinase; Sublingual Gland; Deiodinase; 5'ーdeiodinase

Studies of the thyroid hormone metabolism in the brain have been hampered by its extreme complexity and heterogenity. Thus we tried to establish more simplified systems to study the metabolism and action of thyroid hormone in the brain.We found that type-III 5-deiodinase (5D-III), which specifically inactivates thyroxine and is abundant in the brain, in rat posterior pituitary and pineal gland. The activity in the pituitary was localized in the neural lobe and was not found in the intermediate lobe. These two organs also have type-II 5'-deiodinase (5'D-II), which specifically activates thyroxine. Pineal 5'D-II also has a marked beta-adrenergically mediated nyctohemeral rhythm. Isozyme distribution in these organs are quite similar to that in the brain. These data suggest that thyroid hormone is likely to have previously unrecognized role in these organs and these can be suitable models to study thyroid hormone metabolism in the brain.Most studies on thyroid hormone metabolism in cultured cells have employed glial cells, although 5'D-II were initially reported to be localized in neurons. Astrocytes exibit only 5D-III and 5'D- I, which has low affinity for thyroxine. 5'D-II is induced only after stimulation by dbcAMP. We used cultured neuronal cells and found 5'D-II and 5D-III under steady condition. Thus astrocytes and neurons are likely to belong to different metabolic compartment.Regulatory mechanism of deiodinases are now under study.

甲状腺激素在大脑中代谢的研究一直受到其极端复杂性和异质性的阻碍。本实验在大鼠脑垂体后叶和松果体中发现了特异性失活甲状腺素的Ⅲ型5-脱碘酶（5D-III）。垂体中的活性定位于神经叶，而在中间叶中未发现。这两个器官也有II型5 '-脱碘酶（5' D-II），它特异性激活甲状腺素。松果体5 'D-II也具有显著的β-肾上腺素能介导的昼夜节律。同工酶在这些器官中的分布与脑中的分布十分相似。这些数据表明，甲状腺激素可能有以前未认识到的作用，在这些器官和这些可以是合适的模型来研究甲状腺激素代谢在brain.Most研究甲状腺激素代谢在培养细胞中的神经胶质细胞，虽然5 'D-II最初被报道定位于神经元。星形胶质细胞仅表达5D-III和5 ′ D-I，其对甲状腺素的亲和力较低。5 ′ D-II仅在dbcAMP刺激后才被诱导。我们使用培养的神经细胞，在稳定条件下发现5 ′ D-II和5D-III。因此，星形胶质细胞和神经元可能属于不同的代谢区室。

项目成果

田中 清: "代謝研究法" 新生化学実験法講座(9)ホルモンII東京化学同人. 31-40 (1992)

田中清：《代谢研究方法》新生物化学实验方法教程（9）激素II东京化学同人社31-40（1992）。

Sasaki S et.al.: "A point mutaion of the T3 receptor β1 gene in a kindred of generalized resistance to thyroid hormone" Mol Cell Endocrinol. 84. 159-166 (1992)

Sasaki S 等人：“甲状腺激素普遍耐药性中 T3 受体 β1 基因的点突变”Mol Cell Endocrinol。 84. 159-166 (1992)

田中 清: "甲状腺ホルモン代謝研究法" 新生化学実験講座. (1992)

田中清：《甲状腺激素代谢研究方法》新生物化学实验教程（1992）。

Tanaka K et.al.: "Generalized ressistance to thyroid hormone in a family" Endocrinol Japon. 39. 533-538 (1992)

Tanaka K 等人：“一个家庭对甲状腺激素的普遍抵抗”Endocrinol Japon。

Greer MA et.al.: "Neuroendocrine relations in thyroid hormone metabolism" Thyroid Hormone Metabolism(ed.Wu S-Y)Blackwell Scientific Publishers,Boston MA,USA. 321-335 (1992)

Greer MA 等人：“甲状腺激素代谢中的神经内分泌关系”甲状腺激素代谢（Wu S-Y 编）Blackwell Scientific Publishers，波士顿马萨诸塞州，美国。