Institute of Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig-Holstein, Kiel, Germany.
Institute of Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig-Holstein, Kiel, Germany.
Chem Biol Interact. 2019 Apr 25;303:57-61. doi: 10.1016/j.cbi.2019.02.018. Epub 2019 Feb 21.
The microsomal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) interconverts glucocorticoid receptor-inert cortisone (11-dehydrocorticosterone in rodents) to its receptor-active form cortisol (corticosterone in rodents). Thus, 11β-HSD1 amplifies glucocorticoid action at the tissue level. According to the current literature, dysregulation of glucocorticoid signaling may contribute to the pathogenesis of the metabolic syndrome in which regeneration of cortisol by 11β-HSD1 may be an important factor. This is why the enzyme has been very intensely investigated as a potential therapeutic target to treat metabolic complications such as obesity and diabetes type 2. However, due to controversial results from the various animal and human studies as well as from different findings with regard to tissue-specific expression and activity, the varied results unfortunately do not yield a consistent picture. Therefore, the precise role of 11β-HSD1 in the development of complications associated with the metabolic syndrome has still not been deciphered yet. Overall, the prominent role of this enzyme in the pathogenesis of the metabolic syndrome becomes more and more dubious and therefore further studies are necessary to clarify its role finally. This short review gives an overview on the main contradicting findings on the role of 11β-HSD1 in the development of visceral obesity and diabetes type 2.
微粒体酶 11β-羟甾类脱氢酶 1 型（11β-HSD1）可将糖皮质激素受体失活的皮质酮（在啮齿动物中为 11-去氢皮质酮）转化为其受体活性形式皮质醇（在啮齿动物中为皮质酮）。因此，11β-HSD1 在组织水平上放大了糖皮质激素的作用。根据目前的文献，糖皮质激素信号转导的失调可能导致代谢综合征的发病机制，其中 11β-HSD1 对皮质醇的再生可能是一个重要因素。这就是为什么该酶作为治疗肥胖和 2 型糖尿病等代谢并发症的潜在治疗靶点受到了非常强烈的研究。然而，由于各种动物和人体研究以及关于组织特异性表达和活性的不同发现的结果存在争议，不幸的是，这些不同的结果并没有产生一致的图景。因此，11β-HSD1 在与代谢综合征相关的并发症发展中的确切作用仍未被破译。总的来说，该酶在代谢综合征发病机制中的突出作用变得越来越值得怀疑，因此需要进一步的研究来最终阐明其作用。这篇简短的综述概述了关于 11β-HSD1 在内脏肥胖和 2 型糖尿病发展中的作用的主要矛盾发现。
