Department of Endocrinology, School Of Medicine, Pontificia Universidad Católica De Chile, Santiago 8330074, Chile.
Metabolism. 2011 Dec;60(12):1775-80. doi: 10.1016/j.metabol.2011.05.001. Epub 2011 Jun 24.
11-β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to cortisol, mainly in the liver and visceral adipose tissue (VAT), and has been implicated in several metabolic disorders. The absence of systemic hypercortisolism in central obesity could be due to increased inactivation of cortisol to its tetrahydrometabolites by the hepatic enzymes 5α- and 5β-reductases. Our aim was to assess the expression of the reductases in the liver and of 11β-HSD1 in the liver and VAT in morbidly obese patients and to analyze their association with clinical, anthropometric, and biochemical parameters. Hepatic and VAT samples were obtained during bariatric surgery. 5α- and 5β-reductases, 11β-HSD1, and 18S expression was measured using real-time polymerase chain reaction. Anthropometric and biochemical variables were analyzed. Forty-one patients were recruited (age, 41.8 ± 10.6 years; body mass index, 42.1 ± 6.6 kg/m(2); 71% women). The expression of hepatic 5α- and 5β-reductases was positively correlated (r = +0.53, P = .004), and their expression levels were correlated with hepatic 11β-HSD1 expression (r = +0.61, P < .001 for 5α-reductase and r = +0.50, P < .001 for 5β-reductase). Hepatic 5α-reductase was associated with insulin (r = +0.34, P = .015). Visceral adipose tissue 11β-HSD1 expression was associated with glucose (r = +0.37, P = .025) and insulin (r = +0.54, P = .002). Our results showed that 5α-reductase and VAT 11β-HSD1 expressions were associated with insulinemia. These findings suggest that overexpression of 5α-reductase, through a higher inactivation of cortisol in the liver, could have a protective role in preserving hepatic sensitivity to insulin. The overexpression of liver reductases in obesity could be an adaptive response to an increase in cortisol production by the liver and visceral 11β-HSD1 to avoid systemic hypercortisolism.
11-β-羟类固醇脱氢酶 1 型（11β-HSD1）可将皮质酮转化为皮质醇，主要在肝脏和内脏脂肪组织（VAT）中进行，并且与多种代谢紊乱有关。中心性肥胖患者无全身性皮质醇增多症，可能是由于肝脏的 5α-和 5β-还原酶使皮质醇失活为四氢代谢物增加所致。我们的目的是评估病态肥胖患者肝脏中的还原酶和肝脏及 VAT 中的 11β-HSD1 的表达，并分析其与临床、人体测量和生化参数的关系。在减肥手术期间获得了肝和 VAT 样本。使用实时聚合酶链反应测量 5α-和 5β-还原酶、11β-HSD1 和 18S 的表达。分析了人体测量学和生化变量。招募了 41 名患者（年龄，41.8 ± 10.6 岁；体重指数，42.1 ± 6.6 kg/m2；71%为女性）。肝 5α-和 5β-还原酶的表达呈正相关（r = +0.53，P =.004），并且它们的表达水平与肝 11β-HSD1 的表达相关（r = +0.61，P <.001 用于 5α-还原酶，r = +0.50，P <.001 用于 5β-还原酶）。肝 5α-还原酶与胰岛素相关（r = +0.34，P =.015）。VAT 11β-HSD1 的表达与葡萄糖（r = +0.37，P =.025）和胰岛素（r = +0.54，P =.002）相关。我们的结果表明，5α-还原酶和 VAT 11β-HSD1 的表达与胰岛素血症有关。这些发现表明，通过肝脏中皮质醇失活的增加，5α-还原酶的过度表达可能对维持肝脏对胰岛素的敏感性具有保护作用。肥胖中肝还原酶的过度表达可能是对肝脏和内脏 11β-HSD1 产生的皮质醇增加的适应性反应，以避免全身性皮质醇增多症。
