Transcriptional regulation of the thyrotropin subunit genes by thyroid hormone.
Transcriptional regulation of the thyrotropin subunit genes by thyroid hormone.
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DOI：
10.1016/s0021-9258(18)89450-9
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发表时间：
1985-03
期刊：
影响因子：
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通讯作者：
M. Shupnik;W. Chin;J. Habener;E. Ridgway
中科院分区：
文献类型：
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作者：
M. Shupnik;W. Chin;J. Habener;E. Ridgway
促甲状腺素 (TSH) 是一种垂体糖蛋白，由两个亚基（α 和 β）组成，调节甲状腺产生甲状腺激素。反过来，甲状腺激素对 TSH 的产生产生负反馈。我们研究了三碘甲状腺原氨酸 (T3) 对 TSH 亚基基因转录的影响。每天给携带 TtT 97 促甲状腺肿瘤的甲状腺功能减退 LAF1 小鼠注射 T3（5 微克/100 克体重，腹膜内），并在 0、0.5、1、4 或 120 小时后处死。从肿瘤中分离出细胞核，并在[α-32P]UTP存在的情况下继续进行RNA合成。通过与含有α亚基或TSH-β mRNA特异性序列的固定化克隆cDNA杂交来定量新合成的mRNA序列。 α 亚基和 TSH-β 的 mRNA 合成基础水平相似。体内 T3 治疗仅 30 分钟后，α 亚基（减少 28%）和 TSH-β（减少 61%）的 mRNA 合成均减少。这些降低在 4 小时后达到最大（α 亚基为 75%，TSH-β mRNA 合成为 95% 以上），并且在 T3 治疗的 5 天中保持不变。 mRNA 合成的减少先于组织 mRNA 浓度的减少。我们的研究表明，T3 迅速降低 α 亚基和 TSH-β 基因的转录，并且 TSH-β 基因的转录受到的影响程度比 α 亚基基因更大。
Thyrotropin (TSH), a pituitary glycoprotein, consists of two subunits (alpha and beta), and regulates thyroid hormone production by the thyroid gland. The thyroid hormones, in turn, feedback negatively on TSH production. We have investigated the effect of triiodothyronine (T3) on the transcription of the TSH subunit genes. Hypothyroid LAF1 mice bearing TtT 97 thyrotropic tumors were injected daily with T3 (5 micrograms/100 g of body weight, intraperitoneal) and killed after 0, 0.5, 1, 4, or 120 h. Nuclei were isolated from the tumors and allowed to continue RNA synthesis in the presence of [alpha-32P]UTP. Newly synthesized mRNA sequences were quantitated by hybridization to immobilized cloned cDNA containing sequences specific for either alpha subunit or TSH-beta mRNA. Basal levels of mRNA synthesis were similar for alpha subunit and TSH-beta. After only 30 min of T3 treatment in vivo, mRNA synthesis was decreased for both alpha subunit (by 28%) and TSH-beta (by 61%). These decreases were maximum after 4 h, (75% for alpha subunit, greater than 95% for TSH-beta mRNA synthesis), and were maintained for the 5 days of T3 treatment. Decreases in mRNA synthesis precede decreases in tissue mRNA concentrations. Our studies suggest that T3 rapidly decreases the transcription of both the alpha subunit and TSH-beta genes, and that the transcription of the TSH-beta gene is affected to a greater extent than the alpha subunit gene.