IDENTIFICATION OF A NEW CLASS OF STEROID-HORMONE RECEPTORS

IDENTIFICATION OF A NEW CLASS OF STEROID-HORMONE RECEPTORS
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DOI:
10.1038/331091a0
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发表时间:
1988-01-07
期刊:
影响因子:
64.8
通讯作者:
EVANS, RM
EVANS, RM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
GIGUERE, V;YANG, N;EVANS, RM

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性腺和肾上腺产生的类固醇分为五大类,其中包括雌激素,孕激素,雄激素,糖皮质激素和盐皮质激素。性腺类固醇控制生殖系统的分化和生长,诱导和维持性特征并调节生殖行为。肾上腺类固醇也影响分化以及作为代谢调节剂。每种类固醇的作用主要取决于其特异性受体,因此其性质可以为类固醇激素作用的分类提供基础。人糖皮质激素(hGR)(参考文献1)、雌激素2、3(hER)、孕酮4(hPR)和盐皮质激素5(hMR)受体、互补DNA以及来自不同物种的同源物的成功克隆、测序和表达6 -11,为研究受体结构及其对基因表达的影响提供了第一次机会。序列比较和突变分析12,13显示了所有类固醇激素受体组共有的结构特征。受体共享高度保守的富含半胱氨酸的区域,其作为DNA结合结构域14,15发挥作用。这个共同的片段允许基因组扫描相关的基因产物:例如,使用hGR杂交探针分离hMR cDNA 5。在这项研究中,使用的DNA结合结构域的人雌激素受体cDNA作为杂交探针,我们已经分离出两个cDNA克隆编码多肽的结构特征暗示隐类固醇激素受体,可能参与一个新的激素反应系统。
The gonads and adrenal glands produce steroids classified into five major groups which include the oestrogens, progestins, androgens, glucocorticoids and mineralocorticoids. Gonadal steroids control the differentiation and growth of the reproductive system, induce and maintain sexual characteristics and modulate reproductive behaviour. Adrenal steroids also influence differentiation as well as being metabolic regulators. The effects of each steroid depend primarily on its specific receptors, the nature of which could therefore provide a basis for classification of steroid hormone action. The successful cloning, sequencing and expression of the human glucocorticoid (hGR) (ref. 1), oestrogen2,3(hER), progesterone4 (hPR), and mineralocorticoid5 (hMR) receptors, complementary DNA, plus homologues from various species6–11, provides the first opportunity to study receptor structure and its influence on gene expression. Sequence comparison and mutational analysis12,13show structural features common to all groups of steroid hormone receptors. The receptors share a highly conserved cysteine-rich region which functions as the DNA-binding domain14,15. This common segment allows the genome to be scanned for related gene products: hMR cDNA for example, was isolated using an hGR hybridization probe5. In this study, using the DNA-binding domain of the human oestrogen receptor cDNA as a hybridization probe, we have isolated two cDNA clones encoding polypeptides with structural features suggestive of cryptic steroid hormone receptors which could participate in a new hormone response system.