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The further redefining of steroid-mediated signaling

机译：进一步重新定义类固醇介导的信号传导

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The classical paradigm of steroid hormone action is that intracellular receptors bind to specific steroids to modulate gene expression within the nuclei of target cells. However, increasing evidence now suggests that many important steroid-induced signaling events are triggered independent of transcription. Examples of "nongenomic" biological responses to steroids include estrogen-induced proliferation of breast cell lines, estrogen-mediated dilation of blood vessels, and progesterone-induced activation of the acrosomal reaction in sperm. The signaling mechanisms responsible for these biological responses are diverse, such as activation of signaling molecules Src, extracellular signal-regulated kinase (ERK), endothelial nitricoxide synthase (eNOS), and Akt, as well as rapid alterations in intracellular calcium and cAMP levels. Experiments designed to identify steroid receptors that may modulate these nongenomic processes have produced several candidates, including classical steroid receptors located in the membrane, traditional G protein-coupled receptors (GPCRs) (7, 8), and novel membrane-associated steroid binding proteins. In most cases, however, the true physiologic importance of these receptors has yet to be proven. Two articles by Zhu and colleagues in this issue of PNAS provide new and provocative insight toward identifying potentially physiologically relevant steroid receptors capable of mediating nongenomic signaling, describing a novel family of high-affinity membrane steroid receptors with structure and signaling similar to GPCRs.
机译：类固醇激素作用的经典范例是细胞内受体与特定类固醇结合以调节靶细胞核内的基因表达。但是，现在越来越多的证据表明，许多重要的类固醇诱导的信号转导事件均独立于转录而触发。对类固醇的“非基因组”生物学反应的例子包括雌激素诱导的乳腺细胞系增殖，雌激素介导的血管扩张以及黄体酮诱导的精子顶体反应活化。负责这些生物反应的信号机制是多种多样的，例如信号分子Src，细胞外信号调节激酶（ERK），内皮型一氧化氮合酶（eNOS）和Akt的激活，以及细胞内钙和cAMP水平的快速变化。旨在识别可调节这些非基因组过程的类固醇受体的实验已经产生了几种候选物，包括位于膜上的经典类固醇受体，传统的G蛋白偶联受体（GPCR）（7、8）和新型的膜相关类固醇结合蛋白。然而，在大多数情况下，这些受体的真正生理重要性尚未得到证实。 Zhu和他的同事在本期PNAS上发表的两篇文章为鉴定能够介导非基因组信号传导的潜在生理相关类固醇受体提供了新的具有启发性的见解，描述了一种新型的高亲和力膜类固醇受体家族，其结构和信号传导类似于GPCR。

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