Walker Brian R, Seckl Jonathan R
University of Edinburgh, Endocrinology Unit, Western General Hospital, Edinburgh EH4 2XU, UK.
Expert Opin Ther Targets. 2003 Dec;7(6):771-83. doi: 10.1517/14728222.7.6.771.
11beta-hydroxysteroid dehydrogenase Type 1 (11HSD1) catalyses regeneration of active 11-hydroxy glucocorticoids from inactive 11-keto metabolites within target tissues. Inhibition of 11HSD1 has been proposed as a novel strategy to lower intracellular glucocorticoid concentrations, without affecting circulating glucocorticoid levels and their responsiveness to stress. Increased 11HSD1 activity may be pathogenic, for example, in adipose tissue in obesity. Experiments in transgenic mice and using prototype inhibitors in humans show benefits of 11HSD1 inhibition in liver, adipose and brain tissue in treating features of the metabolic syndrome and cognitive dysfunction with ageing. The clinical development of potent selective 11HSD1 inhibitors is now a high priority.
11β-羟基类固醇脱氢酶1型（11HSD1）催化靶组织内无活性的11-酮代谢产物再生为活性11-羟基糖皮质激素。抑制11HSD1已被提议作为一种降低细胞内糖皮质激素浓度的新策略，而不影响循环糖皮质激素水平及其对应激的反应性。例如，在肥胖症患者的脂肪组织中，11HSD1活性增加可能具有致病性。转基因小鼠实验以及在人体中使用原型抑制剂的实验表明，抑制11HSD1对肝脏、脂肪和脑组织治疗代谢综合征特征及衰老相关认知功能障碍有益。强效选择性11HSD1抑制剂的临床开发目前是当务之急。
