Extra-Nuclear Steroid Receptors: Integration with Multiple Signaling Pathways

描述（由申请人提供）： 类固醇介导的过程传统上被认为是由核受体转录活性的变化来调节。然而，临床线索表明，类固醇也必须独立于转录的信号。例如，肾上腺皮质功能不全患者的糖皮质激素治疗在几分钟内就导致症状缓解-太快了，以至于不涉及转录和随后蛋白质表达的变化。因此，最近的研究已经在质膜上检测到经典的类固醇受体，在那里它们通过激活核外的、不依赖于转录的信号传导途径来发出信号。虽然这些效应的重要性最初受到了健康的怀疑，但核外类固醇受体信号传导领域在过去十年中已经爆炸。类固醇的非基因组作用现在被接受参与调节许多重要的生物学过程，包括增殖、凋亡、血管生成、神经元信号传导和生殖细胞发育。此外，已显示膜起始的和核类固醇受体信号传导协同作用，使得膜起始的类固醇信号传导导致经典类固醇受体的转录增强。最后，类固醇触发的，转录非依赖性，通路的研究揭示了新的信号传导机制，目前正在有针对性地抑制肿瘤依赖性过程。这个FASEB主办的会议的目的是汇集研究人员研究转录独立和依赖类固醇信号，努力促进串扰和合作，以及进一步统一类固醇信号领域。本次会议的三个目的是：1）回顾核外和转录类固醇信号领域令人兴奋的新发现; 2）为年轻的研究人员提供一个场所，展示他们的工作，并与类固醇信号领域的领导者互动; 3）讨论类固醇信号研究的重要转化意义。

DESCRIPTION (provided by applicant): Steroid-mediated processes have traditionally been thought to be regulated by changes in nuclear receptor transcriptional activity. However, clinical clues have suggested that steroids must also signal independent of transcription. For example, glucocorticoid treatment of patients with adrenal insufficiency results in symptomatic relief within minutes - much too rapidly to involve changes in transcription and subsequent protein expression. Accordingly, recent studies have detected classical steroid receptors at the plasma membrane, where they signal through activation of extra-nuclear, transcription-independent signaling pathways. While the importance of these effects was first met with healthy skepticism, the field of extra-nuclear steroid receptor signaling has exploded over the past ten years. Nongenomic actions of steroids are now accepted to participate in regulating many important biological processes, including proliferation, apoptosis, angiogenesis, neuronal signaling, and germ cell development. In addition, membrane-initiated and nuclear steroid receptor signaling have been shown to work in synergy such that membrane-initiated steroid signaling leads to enhanced transcription by classical steroid receptors. Finally, the study of steroid-triggered, transcription-independent, pathways has revealed novel signaling mechanisms that are currently being targeted to suppress hormone-dependent neoplastic processes. The purpose of this FASEB-sponsored conference is to bring together investigators studying both transcription-independent and -dependent steroid signaling in an effort to foster cross talk and collaboration, as well as to further unify the field of steroid signaling. The three aims of this conference are: 1) To review exciting new discoveries in the fields of both extra-nuclear and transcriptional steroid signaling; 2) To provide a venue for young investigators to present their work and interact with established leaders in the field of steroid signaling; and 3) Discuss the important translational implications of steroid signaling research.