Giguère V, Yang N, Segui P, Evans R M
Howard Hughes Medical Institute, Salk Institute for Biological Studies, San Diego, California 92138.
Nature. 1988 Jan 7;331(6151):91-4. doi: 10.1038/331091a0.
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), oestrogen (hER), progesterone (hPR), and mineralocorticoid (hMR) receptors, complementary DNA, plus homologues from various species, provides the first opportunity to study receptor structure and its influence on gene expression. Sequence comparison and mutational analysis show 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 domain. This common segment allows the genome to be scanned for related gene products: hMR cDNA for example, was isolated using an hGR hybridization probe. 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.
性腺和肾上腺分泌的类固醇可分为五大类，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，诱导并维持性征，调节生殖行为。肾上腺类固醇也影响分化，同时还是代谢调节因子。每种类固醇的作用主要取决于其特定受体，因此受体的性质可为类固醇激素作用的分类提供依据。人糖皮质激素（hGR）（参考文献1）、雌激素（hER）、孕激素（hPR）和盐皮质激素（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，为研究受体结构及其对基因表达的影响提供了首个机会。序列比较和突变分析显示了所有类固醇激素受体组共有的结构特征。这些受体共享一个高度保守的富含半胱氨酸的区域，该区域作为DNA结合域发挥作用。这个共同片段使得能够在基因组中搜索相关基因产物：例如，使用hGR杂交探针分离出了hMR cDNA。在本研究中，我们以人雌激素受体cDNA的DNA结合域作为杂交探针，分离出了两个cDNA克隆，它们编码的多肽具有暗示潜在类固醇激素受体的结构特征，这些受体可能参与一个新的激素反应系统。
