HORMONAL REGULATION OF THYROGLOBULIN GENE IN THYROIDS

这项研究的长期目标是阐明 激素调节血管紧张素转换酶基因表达的机制 甲状腺球蛋白(TG)基因，以进一步了解 人甲状腺中该基因的调控问题 肿瘤。甲状腺的不同功能有 主要受脑下垂体激素促甲状腺激素调节 (TSH)。TSH几乎增强了甲状腺细胞的方方面面 代谢包括甲状腺球蛋白(TG)的合成，这是 甲状腺激素生物合成的前体。在一些 甲状腺肿瘤以及一种甲状腺大鼠细胞系(FRTL-5R)， 正常的调节机制被改变，合成 TG与TSH无关。在本申请中，我们建议 促甲状腺激素对甘油三酯基因转录调控机制的研究 以及正常大鼠甲状腺FRTL-5细胞中的其他激素。我们会 TG基因调控区与Tg基因融合构建基因 细菌氯霉素乙酰转移酶(CAT)基因。 将融合基因转移到FRTL-5细胞后，合成 将研究TG基因控制下的CAT。DNA TSH、cAMP、胰岛素和任何其他 激素将通过系统地删除TG来确定 青枯菌的调控序列及缺失突变体的研究 猫基因的激素调节。我们还将调查 与这些元素相互作用的核因子的存在，通过 DNA迁移率改变和DNase I足迹分析。可能的 CAMP的调节亚基(RI和RII)的参与- 依赖的蛋白激酶与TG激素的相互作用- 监管要素也将受到调查。这些信息 从该细胞系中获得的基因将用于研究 高脂血症患者TG基因激素调节机制的变化 人甲状腺肿瘤和变异型FRTL-5细胞系(FRTL-5) 5R)。我们将研究(1)染色质可能的变化 结构；(2)激素调节因子和；(3) 变异型FRTL-5R细胞中的TG调节元件以及 人类甲状腺肿瘤。

The long-term objectives of this research are to elucidate the mechanisms by which hormones regulate the expression of thyroglobulin (TG) gene and to gain further understanding of the problems of control and regulation of this gene in human thyroid tumors. The differentiated functions of the thyroid gland are regulated mainly by the pituitary gland hormone, thyrotropin (TSH). TSH enhances almost every aspect of thyroid cell metabolism including the synthesis of thyroglobulin (TG), the key precursor in the biosynthesis of thyroid hormones. In some thyroid tumors as well as in one thyroid rat cell line (FRTL-5R), the normal regulatory mechanism is altered and the synthesis of TG is independent of TSH. In this application, we propose to study the regulatory mechanisms of TG gene transcription by TSH and other hormones in normal rat thyroid FRTL-5 cells. We will construct genes by fusing the regulatory regions of TG gene with the bacterial chloramphenicol acetyltransferase (CAT) gene. Following transfer of the fused gene to FRTL-5 cells, synthesis of CAT under the control of TG gene will be investigated. The DNA regulatory elements for TSH, cAMP, insulin and any other hormone will be identified by systematic deletions of the TG regulatory sequences and investigation of the deletion mutants on hormone regulation of the CAT gene. We will also investigate the presence of nuclear factors which interact with these elements by DNA mobility shift and DNase I footprinting assay. The possible involvement of the regulatory subunits (RI and RII) of cAMP- dependent protein kinase in interaction with the TG hormonal- regulatory elements will also be investigated. The information obtained from this cell line will be applied to investigation of alterations of hormonal regulatory mechanisms of TG gene in human thyroid tumors and in the variant FRTL-5 cell line (FRTL- 5R). We will examine the possible alterations in (1) chromatin structure; (2) hormone regulatory factors and; (3) sequences of the TG regulatory elements in the variant FRTL-5R cells as well as in human thyroid tumors.