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大鼠生长激素受体和血清结合蛋白信使核糖核酸的组织分布、特性及调控

Tissue distribution, characterization, and regulation of messenger ribonucleic acid for growth hormone receptor and serum binding protein in the rat.

作者信息

Tiong T S, Herington A C

机构信息

Prince Henry's Institute of Medical Research, Monash Medical Centre, Melbourne, Australia.

出版信息

Endocrinology. 1991 Sep;129(3):1628-34. doi: 10.1210/endo-129-3-1628.

DOI:10.1210/endo-129-3-1628
PMID:1874192
Abstract

The distribution of GH receptor (GHR) and GH-binding protein (GHBP) mRNAs in multiple rat tissues was examined by Northern blotting using a cDNA fragment encoding the common extracellular domain of the GHR and the serum GHBP. Both GHR and GHBP mRNAs [4.5 and 1.2 kilobases (kb), respectively] were present in liver, kidney, adrenal, heart, muscle, ovary, mammary gland, gastrointestinal tract, and adipose tissue, but were barely or not detectable in testis, thymus, or brain. These observations suggest that GH exerts direct effects across a broad spectrum of rat tissues. Nuclease protection analysis also confirmed the presence in extrahepatic tissues of a GHR mRNA with up to 50% of the cytoplasmic domain being identical in sequence to that of the hepatic GHR mRNA. This suggests, but does not prove, that different receptor classes with differing intracellular signalling mechanisms may not exist. It is also clear from our studies that liver was the most abundant source of the truncated (1.2 kb) mRNA and is, therefore, believed to be the primary site of GHBP synthesis. Also, more importantly, at least in the rat, it was only GHBP mRNA that was up-regulated to any extent during pregnancy (female vs. pregnant, P less than 0.001). No significant changes were observed in the abundance of the full-length (4.5 kb) GHR mRNA. This pregnancy-related change in GHBP mRNA was also accompanied by a comparable increase in the actual level of measurable serum GHBP (female vs. pregnant, P = 0.005). Little change was seen in hepatic membrane binding. These data suggest that the GHBP and GHR are both widely coexpressed, but that the expression is not always coordinately regulated. This raises the possibility that the GHBP and GHR may have distinct roles in the regulation of GH delivery and action.

摘要

使用编码生长激素受体(GHR)和血清生长激素结合蛋白(GHBP)共同胞外域的cDNA片段,通过Northern印迹法检测了生长激素受体(GHR)和生长激素结合蛋白(GHBP)mRNA在大鼠多种组织中的分布。GHR和GHBP mRNA(分别为4.5和1.2千碱基(kb))存在于肝脏、肾脏、肾上腺、心脏、肌肉、卵巢、乳腺、胃肠道和脂肪组织中,但在睾丸、胸腺或大脑中几乎检测不到或无法检测到。这些观察结果表明,生长激素在大鼠的广泛组织中发挥直接作用。核酸酶保护分析也证实了肝外组织中存在GHR mRNA,其高达50%的胞质域序列与肝GHR mRNA相同。这表明,但并未证明,可能不存在具有不同细胞内信号传导机制的不同受体类别。我们的研究还清楚地表明,肝脏是截短的(1.2 kb)mRNA最丰富的来源,因此被认为是GHBP合成的主要部位。此外,更重要的是,至少在大鼠中,只有GHBP mRNA在怀孕期间有任何程度的上调(雌性与怀孕雌性相比,P<0.001)。全长(4.5 kb)GHR mRNA的丰度未观察到显著变化。GHBP mRNA的这种与妊娠相关的变化还伴随着可测量血清GHBP实际水平的相应增加(雌性与怀孕雌性相比,P = 0.005)。肝细胞膜结合几乎没有变化。这些数据表明,GHBP和GHR都广泛共表达,但表达并不总是协同调节的。这增加了GHBP和GHR在生长激素传递和作用调节中可能具有不同作用的可能性。

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