A Study of Differential Actions of Thyroid Hormone in Its Target

甲状腺激素对其靶标差异作用的研究

• 批准号: 04454558
• 负责人: HASHIZUME Kiyoshi
• 金额: $ 4.48万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454558/
• 关键词: Nuclear receptor(s); Thyroid hormone receptor; Decarcinogenesis; Differentiation; Thyroid hormone-binding protein; Vitamin D; 分化; 甲状腺ホルモン; 受容体; CTBP

Thyroid hormone receptors are known as one of the nuclear receptor family which is important in the cellular proliferation and differentation. We have isolated the NADPH-dependent cytosolic thyroid hormone binding protein, and characterized this protein in previous studies. In the series of our study, we have shown that the protein plays a role not only as a thyroid hormone reservoir but also as a differentiation regulatory factor in the target cells of thyroid hormone.We found that the protein could be induced by the hormones whose receptors are present as c-erb A superfamily, thyroid hormone receptor and vitamin D receptor. The expression induced by these hormones was prominent in the malignant cells rather than in normal cells. In the malignant cells, this protein induced by vitamin D3 actively promoted the differentiation which is related to the function as an inhibitor for intracellular thyroid hormone reservoir.Thus we concluded that the receptor of thyroid hormone plays a multifunctional signal transducer in target cells, at least, in the regulation of differentiation and proliferation.

甲状腺激素受体被称为核受体家族之一，在细胞增殖和分化中发挥重要作用。我们分离出了 NADPH 依赖性胞质甲状腺激素结合蛋白，并在之前的研究中表征了该蛋白。在我们的系列研究中，我们发现该蛋白不仅作为甲状腺激素库，而且作为甲状腺激素靶细胞的分化调节因子。我们发现该蛋白可以被受体为c-erb A超家族、甲状腺激素受体和维生素D受体的激素诱导。这些激素诱导的表达在恶性细胞中比在正常细胞中更为显着。在恶性细胞中，维生素D3诱导的这种蛋白积极促进分化，这与其作为细胞内甲状腺激素库抑制剂的功能有关。由此我们得出结论，甲状腺激素受体在靶细胞中起多功能信号转导作用，至少在调节分化和增殖方面。

项目成果

Ichikawa, K,Hashizume, K.et al.: "Recognition of a 56 kDa protein in partially purified rat hepatic nuclear thyroid hormone receptor." Endocrinol Japonica. Vol.39. 203-207 (1993)

Ichikawa, K,Hashizume, K.等人：“识别部分纯化的大鼠肝核甲状腺激素受体中的 56 kDa 蛋白质。”

Ichikawa,K.,Hashizume,K.,: "Heat shock decreases nuclear transport of 35,3'-tripodo-L thyronine in clone 9 cells" ENDOCRINOLOGY. 130. 2317-2324 (1992)

Ichikawa,K.,Hashizume,K.，：“热休克降低克隆 9 细胞中 35,3-tripodo-L 甲状腺氨酸的核转运”内分泌学。

Nishii Y,Hashizume K,: "Induction of cytosolic triiodo-L-thyronine binding protein by T_3 in prirmary cultured rat hepatocytes" Endocrine Journal. 40. 399-404 (1993)

Nishii Y，Hashizume K，：“在原代培养的大鼠肝细胞中 T_3 诱导胞质三碘-L-甲状腺氨酸结合蛋白”内分泌杂志。

Nishi, Y., Hashizume, K.et al.: "N-butyrate enhances induction of thyroid hormone-responsive protein." Endocrine Journal. Vol.40. 515-529 (1993)

Nishi, Y., Hashizume, K.等人：“N-丁酸盐增强甲状腺激素反应蛋白的诱导。”

橋爪潔志: "甲状腺ホルモン-作用機序" Annual Review内分泌代謝. 145-158 (1992)

Kiyoshi Hashizume：“甲状腺激素 - 作用机制”内分泌学和代谢年度评论 145-158（1992）。