Cole Timothy J
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
Biotechnol Annu Rev. 2006;12:269-300. doi: 10.1016/S1387-2656(06)12008-6.
Glucocorticoids are important endocrine regulators of a wide range of physiological systems ranging from respiratory development, immune function to responses to stress. Glucocorticoids in cells activate the cytoplasmic glucocorticoid receptor (GR) that dimerizes, translocates to the nucleus and functions as a ligand-dependent transcriptional regulator. Synthetic glucocorticoids such as dexamethasone and prednisolone have for decades been the cornerstone for the clinical treatment of inflammatory diseases, such as rheumatoid arthritis and asthma, and in some lymphoid cancers, yet its prolonged use has undesirable side effects such as obesity, diabetes, immune suppression and osteoporosis. Detailed knowledge on the mechanism of GR action has led to the development of novel selective glucocorticoid receptor modulators (SGRMs) that show promise of being efficacious for specific treatments of disease but with fewer side effects. SGRMs promote specific recruitment of transcriptional co-regulators that elicit specific gene responses and show promise of greater efficacy and specificity in treatment of inflammatory diseases and type-2 diabetes.
糖皮质激素是多种生理系统的重要内分泌调节因子，涉及从呼吸发育、免疫功能到应激反应等各个方面。细胞内的糖皮质激素激活细胞质中的糖皮质激素受体（GR），该受体二聚化后转移至细胞核，并作为配体依赖性转录调节因子发挥作用。几十年来，地塞米松和泼尼松龙等合成糖皮质激素一直是类风湿性关节炎和哮喘等炎症性疾病以及某些淋巴癌临床治疗的基石，但其长期使用会产生诸如肥胖、糖尿病、免疫抑制和骨质疏松等不良副作用。对GR作用机制的深入了解促使新型选择性糖皮质激素受体调节剂（SGRM）的研发，这类药物有望在特定疾病治疗中发挥疗效且副作用更少。SGRM促进转录共调节因子的特异性募集，引发特定的基因反应，并在炎症性疾病和2型糖尿病的治疗中展现出更高疗效和特异性的前景。
