INTRODUCTION 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an intracellular enzyme that catalyses conversion of cortisone into cortisol; correspondingly, 11β-HSD1 inhibitors inhibit this conversion. This systematic review focuses on the use of 11β-HSD1 inhibitors in diseases known to be associated with abnormalities in hypothalamic pituitary adrenal (HPA) axis function. METHODS The databases screened for suitable papers were: MedLine, EMBASE, Web of Science, ClinicalTrials.gov, and Cochrane Central. RESULTS 1925 papers were identified, of which 29 were included in the final narrative synthesis. 11β-HSD1 and its inhibitors have been studied in diabetes, obesity, metabolic syndrome (MetS), and Alzheimer's disease (AD). Higher expression of 11β-HSD1 is seen in obesity and MetS, but has not yet been described in obesity or AD. Genetic studies identify 11β-HSD1 SNPs of interest in populations with diabetes, MetS, and AD. One phase II trial successfully reduced HbA1c in a diabetic population, however trials in MetS, obesity, and AD have not met primary endpoints. CONCLUSIONS Translation of this research from preclinical studies has proved challenging so far, however this is a growing area of research and more studies should focus on understanding the complex relationships between 11β-HSD1 and disease pathology, especially given the therapeutic potential of 11β-HSD1 inhibitors in development.

中文翻译：

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11β-羟基类固醇脱氢酶1型抑制剂在人类疾病中的应用-系统综述和叙述性合成。

引言1型11β-羟基类固醇脱氢酶（11β-HSD1）是一种细胞内酶，可催化可的松转化为皮质醇。相应地，11β-HSD1抑制剂抑制了这种转化。本系统综述着重于在已知与下丘脑垂体肾上腺（HPA）轴功能异常有关的疾病中使用11β-HSD1抑制剂。方法筛选合适论文的数据库为：MedLine，EMBASE，Web of Science，ClinicalTrials.gov和Cochrane Central。结果鉴定出1925篇论文，其中29篇包含在最终的叙事综合中。已经在糖尿病，肥胖症，代谢综合征（MetS）和阿尔茨海默氏病（AD）中研究了11β-HSD1及其抑制剂。在肥胖症和MetS中可见11β-HSD1的高表达，但在肥胖症或AD中尚未被描述。遗传学研究确定了糖尿病，MetS和AD人群中感兴趣的11β-HSD1SNP。一项II期临床试验成功降低了糖尿病人群中的HbA1c，但是在MetS，肥胖症和AD中的试验尚未达到主要终点。结论迄今为止，该临床前研究的翻译工作被证明具有挑战性，但是，这是一个不断发展的研究领域，更多的研究应侧重于理解11β-HSD1与疾病病理之间的复杂关系，尤其是考虑到11β-HSD1抑制剂的治疗潜力开发中。