Glucocorticoid action on target tissues is determined by the density of "nuclear" receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental "programming." The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues.

中文翻译：

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11β-羟基类固醇脱氢酶：组织糖皮质激素作用的细胞内看门人。

糖皮质激素对靶组织的作用取决于“核”受体的密度和 11β-羟基类固醇脱氢酶 (11β-HSD) 的两种同工酶的细胞内代谢，该酶催化活性皮质醇和皮质酮与惰性可的松和 11-脱氢皮质酮的相互转化。11β-HSD 1 型是大多数完整细胞中的主要还原酶，它催化活性糖皮质激素的再生，从而放大细胞作用。11β-HSD1 广泛表达于肝脏、脂肪组织、肌肉、胰岛、成人大脑、炎症细胞和性腺中。11β-HSD1 在肥胖的脂肪组织中选择性升高，导致代谢并发症。同样，11β-HSD1 在老化的大脑中升高，加剧了糖皮质激素相关的认知能力下降。11β-HSD1 的缺乏或选择性抑制可改善啮齿动物模型和人体临床试验中的多种代谢综合征参数，并且随着年龄的增长同样改善认知功能。抑制剂在人类治疗中的功效仍不清楚。11β-HSD2 是一种高亲和力脱氢酶，可使糖皮质激素失活。在远端肾单位，11β-HSD2 确保只有醛固酮是盐皮质激素受体 (MR) 的激动剂。由于肾 MR 的糖皮质激素激活不当，11β-HSD2 抑制或遗传缺陷导致明显的盐皮质激素过量和高血压。胎盘和胎儿也高度表达 11β-HSD2，它通过使糖皮质激素失活，防止胎儿组织过早成熟和随之而来的发育“程序化”。正在探索 11β-HSD2 作为编程标记的作用。因此，11β-HSDs 阐明了内分泌控制的新兴生物学，为人类发病机制提供了重要见解，并提供了新的组织限制治疗途径。