Distribution and abundance of messenger ribonucleic acid for growth hormone receptor isoforms in human tissues
Distribution and abundance of messenger ribonucleic acid for growth hormone receptor isoforms in human tissues
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DOI：
10.1210/jc.85.8.2865
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发表时间：
2000-08-01
影响因子：
5.8
通讯作者：
Ho, KKY
中科院分区：
文献类型：
--
作者：
Ballesteros, M;Leung, KC;Ho, KKY
最近在肝脏中发现了人生长激素受体（GHR）信使核糖核酸（mRNA）的两种可变剪接外显子9变体，GHR-（1-279）和GHR-（1-277）。它们编码缺乏大部分细胞内结构域的受体蛋白，并以显性负性方式抑制GH作用。关于这些GHR异构体的组织分布和丰度知之甚少。我们已经开发了针对全长和截短的GHR的定量RT-PCR检测方法，并研究了它们在各种人体组织和细胞系中的表达，全长GHR和GHR-（1-279）的mRNA在所研究的所有组织中都很容易检测到，其中肝脏、脂肪、肌肉和肾脏显示出高水平的表达。这两种受体亚型也在一系列人类细胞系中检测到，在淋巴母细胞样细胞系IM 9中表达最强。相反，GHR-（1-277）信使在肝脏、脂肪、肌肉、肾脏和前列腺中的表达水平较低，在IM 9细胞中的表达量很低。然而，肝脏的全长受体mRNA和GHR-（1-277）mRNA比脂肪和肌肉多2- 4倍，而GHR-（1- 279）的mRNA水平在三种组织中相似。GHR-（1-279）在肝脏中占不到4%，在脂肪和肌肉中占7-10%。GHR-（1-277）占肝脏中GHR总转录本的0.5%，在其他两种组织中不到0.1%。这些数据表明，绝对和相对丰度的三个GHR异构体的mRNA可能是组织特异性。外显子9选择性剪接GHR变体表达的调节可能为组织水平GH敏感性的调节提供了潜在的机制。
Two alternatively spliced exon 9 variants of human GH receptor (GHR) messenger ribonucleic acid (mRNA), GHR-(1-279) and GHR-(1-277), were recently identified in liver. They encode receptor proteins lacking most of the intracellular domain and inhibit GH action in a dominant negative manner. Little is known about tissue distribution and abundance of these GHR isoforms. We have developed quantitative RT-PCR assays specific for the full-length and truncated GHRs and investigated their expression in various human tissues and cell lines.The mRNA of full-length GHR and GHR-(1-279) were readily detectable in all tissues investigated, with liver, fat, muscle, and kidney showing high levels of expression. These two receptor isoforms were also detected in a range of human cell lines, with strongest expression in IM9, a lymphoblastoid cell line. In contrast, GHR-(1-277) message was expressed at low levels in liver, fat, muscle, kidney, and prostate and in trace amount in IM9 cells.Full-length GHR was the most abundant isoform, accounting for over 90% of total receptor transcripts in liver, fat, and muscle for quantitative RT-PCR. However, liver had 2- to 4-fold more full-length receptor mRNA and 16- to 40-fold more GHR-(1-277) mRNA than fat and muscle, whereas the mRNA levels of GHR-(1-279) were similar in the three tissues. GHR-(1-279) constituted less than 4% in liver and 7-10% in fat and muscle. GHR-(1-277) accounted for 0.5% of total GHR transcripts in liver and less than 0.1% in the other two tissues. These data suggest that the absolute and relative abundance of mRNA of the three GHR isoforms may be tissue specific. The regulation of expression of exon 9 alternatively spliced GHR variants may provide a potential mechanism for modulation of GH sensitivity at the tissue level.