SXR, a novel steroid and xenobiotic-sensing nuclear receptor
SXR, a novel steroid and xenobiotic-sensing nuclear receptor
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DOI：
10.1101/gad.12.20.3195
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发表时间：
1998-10-15
影响因子：
10.5
通讯作者：
Evans, RM
中科院分区：
文献类型：
--
作者：
Blumberg, B;Sabbagh, W;Evans, RM
生理动态平衡的一个重要要求是对内源激素和具有生物活性的外来化合物进行解毒和清除。许多解毒作用是由细胞色素P-450酶执行的，其中许多酶具有广泛的底物特异性，可以被数百种不同的化合物诱导，包括类固醇。摄入饮食中的类固醇和类脂会诱导相同的酶；因此，它们似乎整合到一个协调的代谢途径中。我们不再拥有数百个受体，每个诱导化合物一个，我们建议存在几个广泛的特异性、低亲和力的传感受体，这些受体将监测诱导剂的总水平，以触发代谢酶的产生。为了支持这一模型，黑麦已经分离出一种新的核受体，称为类固醇和异种生物受体(SXR)，它激活转录，对各种天然和合成化合物做出反应。SXR与RXR形成异二聚体，可与类固醇诱导的细胞色素P-450基因中的反应元件结合并诱导转录，并在表达这些分解代谢酶的组织中表达。这些结果有力地支持了类固醇感受器假说，并提示广谱的特异性感受器可能代表核受体超家族的一个新分支。
An important requirement for physiologic homeostasis is the detoxification and removal of endogenous hormones and xenobiotic compounds with biological activity. Much of the detoxification is performed by cytochrome P-450 enzymes, many of which have broad substrate specificity and are inducible by hundreds of different compounds, including steroids. The ingestion of dietary steroids and lipids induces the same enzymes; therefore, they would appear to be integrated into a coordinated metabolic pathway. Instead of possessing hundreds of receptors, one for each inducing compound, we propose the existence of a few broad specificity, low-affinity sensing receptors that would monitor aggregate levels of inducers to trigger production of metabolizing enzymes. In support of this model, rye have isolated a novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), which activates transcription in response to a diversity of natural and synthetic compounds. SXR forms a heterodimer with RXR that can bind to and induce transcription from response elements present in steroid-inducible cytochrome P-450 genes and is expressed in tissues in which these catabolic enzymes are expressed. These results strongly support the steroid sensor hypothesis and suggest that broad specificity sensing receptors may represent a novel branch of the nuclear receptor superfamily.