Mounting evidence suggests that--beyond the well-known genomic effects--glucocorticoids affect cell function via non-genomic mechanisms. Such mechanisms operate in many major systems and organs including the cardiovascular, immune, endocrine and nervous systems, smooth and skeletal muscles, liver, and fat cells. Non-genomic effects are exerted by direct actions on membrane lipids (affecting membrane fluidity), membrane proteins (e.g. ion channels and neurotransmitter receptors), and cytoplasmic proteins (e.g. MAPKs, phospholipases, protein kinases, etc.). These actions are mediated by the glucocorticoids per se or by the proteins dissociated from the liganded glucocorticoid receptor complex. The MR and GR also activate non-genomic mechanisms in certain cases. Some effects of glucocorticoids are shared by a variety of steroids, whereas others are more selective. Moreover, "ultra-selective" effects-mediated by certain glucocorticoids only-were also shown. Disparate findings suggest that non-genomic mechanisms also show "demand-specificity", i.e. require the coincidence of two or more processes. Some of the non-genomic mechanisms activated by glucocorticoids are therapeutically relevant; moreover, the "non-genomic specificity" of certain glucocorticoids raises the possibility of therapeutic applications. Despite the large body of evidence, however, the non-genomic mechanisms of glucocorticoids are still poorly understood. Criteria for differentiating genomic and non-genomic mechanisms are often loosely applied; interactions between various mechanisms are unknown, and non-genomic mechanism-specific pharmacological (potentially therapeutic) agents are lacking. Nevertheless, the discovery of non-genomic mechanisms is a major breakthrough in stress research, and further insights into these mechanisms may open novel approaches for the therapy of various diseases.

中文翻译：

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非基因组糖皮质激素机制对身体功能和中枢神经系统的影响。对结果的批判性评估

越来越多的证据表明——除了众所周知的基因组效应之外——糖皮质激素通过非基因组机制影响细胞功能。这种机制在许多主要系统和器官中起作用，包括心血管、免疫、内分泌和神经系统、平滑肌和骨骼肌、肝脏和脂肪细胞。非基因组效应通过对膜脂（影响膜流动性）、膜蛋白（例如离子通道和神经递质受体）和细胞质蛋白（例如 MAPK、磷脂酶、蛋白激酶等）的直接作用而发挥。这些作用由糖皮质激素本身或从配体的糖皮质激素受体复合物解离的蛋白质介导。在某些情况下，MR 和 GR 也会激活非基因组机制。糖皮质激素的某些作用由多种类固醇共享，而其他人则更具选择性。此外，还显示了仅由某些糖皮质激素介导的“超选择性”效应。不同的研究结果表明，非基因组机制也表现出“需求特异性”，即需要两个或多个过程的巧合。一些由糖皮质激素激活的非基因组机制具有治疗相关性；此外，某些糖皮质激素的“非基因组特异性”提高了治疗应用的可能性。然而，尽管有大量证据，糖皮质激素的非基因组机制仍知之甚少。区分基因组和非基因组机制的标准经常被松散地应用；各种机制之间的相互作用是未知的，并且缺乏非基因组机制特异性药理学（潜在治疗）药物。尽管如此，非基因组机制的发现是应激研究的重大突破，进一步了解这些机制可能为各种疾病的治疗开辟新的途径。