Tissue distribution and quantitative analysis of estrogen receptor-alpha (ER alpha) and estrogen receptor-beta (ER beta) messenger ribonucleic acid in the wild-type and ER alpha-knockout mouse
Tissue distribution and quantitative analysis of estrogen receptor-alpha (ER alpha) and estrogen receptor-beta (ER beta) messenger ribonucleic acid in the wild-type and ER alpha-knockout mouse
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DOI：
10.1210/en.138.11.4613
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发表时间：
1997-11-01
期刊：
影响因子：
4.8
通讯作者：
Korach, KS
中科院分区：
文献类型：
--
作者：
Couse, JF;Lindzey, J;Korach, KS
直到最近，只有一种类型的雌激素受体（ER）被认为存在并介导哺乳动物组织中激素17 β-雌二醇的基因组效应。然而，从小鼠、大鼠和人类中克隆编码第二种ER（称为ERP）的基因，促使人们重新评估雌激素信号系统。基于体外研究，ERP蛋白以与经典ER（现称为ER α）相似的亲和力结合雌二醇，并且能够介导雌二醇在转染的哺乳动物细胞系中的作用。对于进一步研究ERP的可能生理作用及其与ER α的可能相互作用至关重要的是两种ER类型的组织分布数据。在此，我们已经描述了能够检测和区分信使RNA（mRNA）转录物与小鼠中ER α和ER β基因的RNA酶保护测定的优化和使用。因为该测定是直接定量的，所以可以比较各种组织内的表达水平。此外，还使用ER α敲除（ERKO）小鼠研究了ER α基因的破坏对ERP基因表达的影响。在两种性别的所有野生型组织中均检测到编码ER α的转录物。在雌性生殖道中，在卵巢中观察到ER β mRNA的最高表达，并且在个体动物中表现出很大的差异;在子宫和输卵管中观察到可检测水平，而乳腺组织为阴性。在雄性生殖道中，在前列腺和附睾中观察到ERP的显著表达，而睾丸为阴性。在两种性别的其他组织中，下丘脑和肺中ER α和ER β mRNA均明显阳性。ERKO小鼠卵巢、前列腺和附睾中ER β mRNA水平略有降低。这些数据，结合在两种性别的ERKO小鼠中描述的几种表型，表明ER β蛋白的生物学功能可能取决于某些细胞类型和组织中ER α的存在。ERKO小鼠生理表型的进一步表征可能阐明可能的ER β特异性作用。
Until recently, only a single type of estrogen receptor (ER) was thought to exist and mediate the genomic effects of the hormone 17 beta-estradiol in mammalian tissues. However, the cloning of a gene encoding a second type of ER, termed ERP, from the mouse, rat, and human has prompted a reevaluation of the estrogen signaling system. Based on in vitro studies, the ERP protein binds estradiol with an affinity similar to that of the classical ER (now referred to as ER alpha) and is able to mediate the effects of estradiol in transfected mammalian cell lines. Essential to further investigations of the possible physiological roles of ERP, and its possible interactions with ER alpha, are data on the tissue distribution of the two ER types. Herein, we have described the optimization and use of an RNase protection assay able to detect and distinguish messenger RNA (mRNA) transcripts from both the ER alpha and ER beta genes in the mouse. Because this assay is directly quantitative, a comparison of the levels of expression within various tissues was possible. In addition, the effect of disruption of the ER alpha gene on the expression of the ERP gene was also investigated using the ER alpha-knockout (ERKO) mouse. Transcripts encoding ER alpha were detected in all the wild-type tissues assayed from both sexes. In the female reproductive tract, the highest expression of ER beta mRNA was observed in the ovary and showed great variation among individual animals; detectable levels were observed in the uterus and oviduct, whereas mammary tissue was negative. In the male reproductive tract, significant expression of ERP was seen in the prostate and epididymis, whereas the testes were negative. In other tissues of both sexes, the hypothalamus and lung were clearly positive for both ER alpha and ER beta mRNA. The ERKO mice demonstrated slightly reduced levels of ER beta mRNA in the ovary, prostate, and epididymis. These data, in combination with the several described phenotypes in both sexes of the ERKO mouse, suggest that the biological functions of the ER beta protein may be dependent on the presence of ER alpha in certain cell types and tissues. Further characterization of the physiological phenotypes in the ERKO mice may elucidate possible ER beta specific actions.