Multiple actions of steroid hormones--a focus on rapid, nongenomic effects.
Multiple actions of steroid hormones--a focus on rapid, nongenomic effects.
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DOI：
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发表时间：
2000-12
影响因子：
21.1
通讯作者：
E. Falkenstein;H. Tillmann;M. Christ;M. Feuring;M. Wehling
中科院分区：
文献类型：
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作者：
E. Falkenstein;H. Tillmann;M. Christ;M. Feuring;M. Wehling
根据传统模型，类固醇激素结合细胞内受体，随后调节转录和蛋白质合成，从而触发最终导致延迟效应的基因组事件。基于分子结构的相似性，类固醇、维生素D（3）衍生物、甲状腺激素、类维生素A和各种孤儿受体的特异性受体被认为代表类固醇受体的超家族。此外，已广泛认识到主要影响细胞内信号传导的类固醇的非常快速的作用，这显然与基因组模型不相容。这些快速的非基因组类固醇作用可能通过特定的膜受体传递。非基因组类固醇效应和不同受体的证据涉及所有类固醇组，包括相关化合物，如维生素D（3）和甲状腺激素。这些快速效应的生理和临床相关性在很大程度上仍不清楚，但它们在体内的存在已在包括人体研究在内的各种环境中得到明确显示。特异性影响非基因组类固醇作用的药物可能在各种临床领域如心血管和中枢神经疾病、电解质稳态和不育症中找到应用。除了基因组类固醇作用的简短描述，这篇综述特别注意非基因组类固醇作用机制的现有知识和重要结果。讨论了其潜在的生理或病理生理相关性和基因组和非基因组反应之间的串扰的作用模式。
According to the traditional model, steroid hormones bind to intracellular receptors and subsequently modulate transcription and protein synthesis, thus triggering genomic events finally responsible for delayed effects. Based upon similarities in molecular structure, specific receptors for steroids, vitamin D(3) derivatives, thyroid hormone, retinoids, and a variety of orphan receptors are considered to represent a superfamily of steroid receptors. In addition, very rapid effects of steroids mainly affecting intracellular signaling have been widely recognized that are clearly incompatible with the genomic model. These rapid, nongenomic steroid actions are likely to be transmitted via specific membrane receptors. Evidence for nongenomic steroid effects and distinct receptors involved is presented for all steroid groups including related compounds like vitamin D(3) and thyroid hormones. The physiological and clinical relevance of these rapid effects is still largely unclear, but their existence in vivo has been clearly shown in various settings including human studies. Drugs that specifically affect nongenomic steroid action may find applications in various clinical areas such as cardiovascular and central nervous disorders, electrolyte homeostasis, and infertility. In addition to a short description of genomic steroid action, this review pays particular attention to the current knowledge and important results on the mechanisms of nongenomic steroid action. The modes of action are discussed in relation to their potential physiological or pathophysiological relevance and with regard to a cross-talk between genomic and nongenomic responses.