A novel transcript for the thyrotropin-releasing hormone receptor in human pituitary and pituitary tumors.

A novel transcript for the thyrotropin-releasing hormone receptor in human pituitary and pituitary tumors.
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人类垂体和垂体肿瘤中促甲状腺素释放激素受体的新转录本。

DOI:
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发表时间:
1997
影响因子:
5.8
通讯作者:
M. Mori
M. Mori
中科院分区:
医学2区
文献类型:
--
作者:
M. Yamada;K. Hashimoto;T. Satoh;N. Shibusawa;H. Kohga;Y. Ozawa;S. Yamada;M. Mori

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我们测定了人正常垂体和垂体肿瘤中TRH受体(TRHR)信使核糖核酸(mRNA)的含量,发现了TRHR基因的一种新转录本。竞争性PCR显示TRHR mRNA的表达在所有垂体腺瘤检查,其水平是可变的,在正常垂体相似。当通过PCR扩增C-末端区域时,观察到另外的短产物。该短片段的克隆和序列分析显示,缺失的序列与第3号外显子的5 '端序列完全对应,表明TRHR mRNA存在选择性剪接。这种选择性剪接导致移码,翻译产生C-末端截短蛋白(HTRHR 2)。HTRHR 2在中国仓鼠卵巢细胞中的表达分析显示与[3 HIMeTRH]无显著结合或细胞内钙对TRH给药的反应。然而,HTRHR 2与野生型(HTRHR 1)的mRNA比例在垂体瘤中存在显著差异。在泌乳素瘤中观察到最高的比率(30%),并且在GH产生肿瘤中几乎没有发现可检测的表达。这些研究结果表明,这种新的人类TRH受体基因的转录本产生的肿瘤特异性的方式,并可能是一个有用的参数,用于评估个人垂体瘤。
We measured the amounts of TRH receptor (TRHR) messenger ribonucleic acid (mRNA) in human normal pituitary and pituitary tumors and found a novel transcript of the TRHR gene. Competitive PCR revealed expression of the TRHR mRNA in all pituitary adenomas examined, and its level was variable and similar to that in the normal pituitary. When the C-terminal region was amplified by PCR, an additional short product was observed. Cloning and sequence analysis of this short fragment revealed that the deleted sequence corresponded exactly to the 5'-sequence of exon 3, indicating alternative splicing of the TRHR mRNA. This alternative splicing resulted in a frame shift, yielding a C-terminal truncated protein (HTRHR2) on translation. Expression analysis of HTRHR2 in Chinese hamster ovary cells showed no significant binding to [3HIMeTRH or response of intracellular calcium to TRH administration. However, the mRNA ratio of HTRHR2 vs. the wild type (HTRHR1) was significantly different among pituitary tumors. The highest ratio was observed in prolactinomas (30%), and almost no detectable expression was found in GH-producing tumors. These findings indicate that this novel transcript of the human TRH receptor gene is produced in a tumor-specific manner and may be a useful parameter for evaluation of individual pituitary tumors.
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影响因子: 5.8
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编码人前促甲状腺素释放激素的人基因组 DNA 和下丘脑 cDNA 的克隆和结构。
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