Schlattner Uwe, Vafopoulou Xanthe, Steel Colin G H, Hormann Robert E, Lezzi Markus
Institute of Cell Biology, ETH Zurich, CH-8093 Zurich, Switzerland.
Mol Cell Endocrinol. 2006 Mar 9;247(1-2):64-72. doi: 10.1016/j.mce.2005.12.051. Epub 2006 Feb 7.
The ecdysteroids (Ec), invertebrate steroid hormones, elicit genomic but also non-genomic effects. By analogy to vertebrates, non-genomic responses towards Ec may be mediated not only by distinct membrane-integrated but also by membrane-associated receptors like the classical nuclear ecdysteroid receptor (EcR) of arthropods. This is supported by a comparison of physiological properties between invertebrate and vertebrate steroid hormone systems and recent findings on the subcellular localization of EcR. The measured or predicted high degree of conformational flexibility of both Ec and the ligand binding domain (LBD) of EcR give rise to a conformational compatibility model: the compatibility between conformations of the cognate receptor's ligand binding domain and structures or conformations of the ligand would determine their interaction and eventually the initiation of genomic versus non-genomic pathways. This model could also explain why specific non-genomic effects are generally not observed with non-steroidal agonists of the bisacylhydrazine group.
蜕皮甾体（Ec）是无脊椎动物的甾体激素，可引发基因组效应，也可引发非基因组效应。与脊椎动物类似，对Ec的非基因组反应可能不仅由独特的膜整合受体介导，还可由膜相关受体介导，如节肢动物的经典核蜕皮甾体受体（EcR）。无脊椎动物和脊椎动物甾体激素系统生理特性的比较以及EcR亚细胞定位的最新研究结果支持了这一观点。所测得的或预测的Ec以及EcR配体结合域（LBD）的高度构象灵活性产生了一种构象兼容性模型：同源受体配体结合域的构象与配体的结构或构象之间的兼容性将决定它们的相互作用，并最终决定基因组途径与非基因组途径的启动。该模型还可以解释为什么通常不会观察到双酰肼类非甾体激动剂产生特定的非基因组效应。
