Photosensitive Steroids as Probes of Estrogen Receptor Sites *
Photosensitive Steroids as Probes of Estrogen Receptor Sites *
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光敏类固醇作为雌激素受体位点的探针*
DOI：
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发表时间：
1980
影响因子：
5.2
通讯作者：
K. Carlson
中科院分区：
文献类型：
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作者：
J. Katzenellenbogen;M. Kilbourn;K. Carlson
类固醇激素受体是在靶组织细胞的细胞质中发现的具有高亲和力和高选择性结合类固醇能力的蛋白质。最初的类固醇受体复合物，在细胞质中形成，经历一个激活过程，之后它进入细胞核并与染色质相互作用。尽管人们对这种染色质相互作用知之甚少，但人们认为它会导致基因表达的变化，这些变化最终反映在组织对激素反应的生化和生理变化中。“亲和标记对我们理解类固醇激素和受体之间相互作用的复杂性以及受体本身的作用做出了重大贡献。”“类固醇受体，即使在最丰富的组织来源中，也是次要的细胞成分，其纯化因其热不稳定性和聚集倾向而变得复杂。”因此，一种能与受体共价结合的放射性标记配体将对受体的纯化和表征有很大的帮助。类固醇受体也以不同的状态存在（未配体、配体和未激活、配体和激活），并在不同的亚细胞间移动。像光亲和标记这样的过程，可以诱导类固醇衍生物在最初与受体结合后的一段时间内以共价方式附着在受体上，这将提供一种独特的方式来跟踪类固醇受体相互作用的动态特征：激活、亚细胞再分配、染色质相互作用、受体再循环和受体降解。最后，类固醇受体有很大的结合倾向，其结果是其表面的物理化学性质可能在纯化后发生变化。这让人怀疑，使用纯化元件在体外重建类固醇、受体和染色质结合位点之间的细胞相互作用，是否会导致体内相互作用的准确表征。能够进行共价标记的光激活类固醇类似物可能被证明是探索某些完整系统（例如培养细胞）中受体作用的重要途径。因此，努力开发类固醇受体亲和标记剂的最终目标应该是获得具有足够选择性和效率的试剂，为系统中受体的共价标记提供足够的手段
Receptors for steroid hormones are those proteins found in the cytoplasm of target tissue cells that have the ability to bind steroids with high affinity and great selectivity. The initial steroid-receptor complex, which forms in the cytoplasm, undergoes an activation process, after which it moves into the nucleus and interacts with chromatin. This chromatin interaction, while still poorly understood, is thought to result in changes in gene expression that are ultimately reflected in the biochemical and physiological alterations that are characteristic of the tissue’s response to the hormone.’ Affinity labeling stands to make a substantial contribution to our understanding of the intricacies of both the interaction between steroid hormones and receptors and the actions of the receptors themselves.’ Steroid receptors, even in the richest tissue sources, are minor cellular constituents, whose purification is complicated by their thermal lability and their tendency to aggregate. Thus, a radiolabeled ligand that could be covalently attached to the receptor would be of great assistance to efforts directed toward the purification and characterization of receptors. Steroid receptors also exist in different states (unliganded, liganded and unactivated, liganded and activated), and move between different subcellular compartments. A process such as photoaffinity labeling, whereby a steroid derivative could be induced to attach covalently to a receptor a t some time subsequent to its initial binding to the receptor, would provide a unique way of following the dynamic features of steroid receptor interaction: activation, subcellular redistribution, chromatin interaction, receptor recycling, and receptor degradation. Finally, steroid receptors have a great tendency towards association, with the result that their apparent physicochemical properties may change upon purification. This causes one to doubt that attempts a t reconstituting the cellular interactions between steroids, receptors, and chromatin binding sites in vitro, using purified elements, will result in accurate representations of the in vivo interaction. Photoactivated steroid analogs capable of covalent labeling may prove to be an important avenue for the exploration of receptor action in certain intact systems (e.g., cells in culture). Thus, the ultimate goal of efforts to develop affinity labeling agents for steroid receptors should be to obtain agents with sufficient selectivity and efficiency to provide adequate means for covalent labeling of receptors in systems that are