Tomlinson J W
Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK.
Minerva Endocrinol. 2005 Mar;30(1):37-46.
Patients with cortisol excess, Cushing's syndrome, develop a classical phenotype characterized by central obesity, hypertension, and increased cardiovascular mortality. Whilst this observation points to the importance of glucocorticoids, circulating cortisol excess is rare and does not explain the pathogenesis of many common conditions. At a tissue specific level, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) locally regenerates active cortisol from inactive cortisone amplifying glucocorticoid receptor activation in the context of normal circulating cortisol levels. Increased 11beta-HSD1 activity and expression have been implicated in the pathogenesis of many common conditions including, obesity, insulin resistance, the metabolic syndrome, polycystic ovarian syndrome, osteoporosis and glaucoma. Furthermore, selective 11beta-HSD1 inhibition has been proposed as a novel therapeutic strategy in many of these conditions. Here we review the role of 11beta-HSD1 in human disease and discuss the impact of selective 11beta-HSD1 inhibition.
患有皮质醇增多症（库欣综合征）的患者会出现以向心性肥胖、高血压和心血管死亡率增加为特征的典型表型。虽然这一观察结果表明了糖皮质激素的重要性，但循环皮质醇增多症较为罕见，且无法解释许多常见病症的发病机制。在组织特异性水平上，11β-羟基类固醇脱氢酶1型（11β-HSD1）在正常循环皮质醇水平的情况下，可将无活性的可的松局部再生为活性皮质醇，从而增强糖皮质激素受体的激活。11β-HSD1活性和表达的增加与许多常见病症的发病机制有关，包括肥胖、胰岛素抵抗、代谢综合征、多囊卵巢综合征、骨质疏松症和青光眼。此外，选择性抑制11β-HSD1已被提议作为治疗这些病症的一种新策略。在此，我们综述了11β-HSD1在人类疾病中的作用，并讨论了选择性抑制11β-HSD1的影响。
