Steroid Hormones Section, NIDDK/LERB, National Institutes of Health, Bethesda, MD, United States.
Mol Cell Endocrinol. 2013 Aug 25;376(1-2):81-4. doi: 10.1016/j.mce.2013.06.007. Epub 2013 Jun 17.
Steroid hormones, acting through their cognate receptor proteins, see widespread clinical applications due to their ability to alter the induction or repression of numerous genes. However, steroid usage is limited by the current inability to control off-target, or non-specific, side-effects. Recent results from three separate areas of research with glucocorticoid and other steroid receptors (cofactor-induced changes in receptor structure, the ability of ligands to alter remote regions of receptor structure, and how cofactor concentration affects both ligand potency and efficacy) indicate that a key element of receptor activity is the intrinsically disordered amino-terminal domain. These results are combined to construct a novel framework within which to logically pursue various approaches that could afford increased selectivity in steroid-based therapies.
甾体激素通过其同源受体蛋白发挥作用，由于能够改变众多基因的诱导或抑制，因此在临床上得到了广泛的应用。然而，由于目前无法控制非特异性副作用，甾体激素的使用受到了限制。最近在糖皮质激素和其他甾体激素受体的三个独立研究领域的结果（共激活因子诱导受体结构改变、配体改变受体结构远程区域的能力，以及共激活因子浓度如何影响配体效力和效能）表明，受体活性的一个关键因素是固有无序的氨基末端结构域。这些结果结合在一起，构建了一个新的框架，可以合理地探索各种方法，从而在基于甾体的治疗中提高选择性。
