Mattsson Cecilia, Rask Eva, Carlström Kjell, Andersson Jonas, Eliasson Mats, Ahrén Bo, Söderberg Stefan, Olsson Tommy
Department of Public Health and Clinical Medicine, Umeå University Hospital, S-901 85 Umeå, Sweden.
Obesity (Silver Spring). 2007 Apr;15(4):887-94. doi: 10.1038/oby.2007.587.
Reduction of cortisone to cortisol is mediated by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), a putative key enzyme in obesity-related complications. Experimental studies suggest that adipokines, notably leptin and tumor necrosis factor-alpha (TNF-alpha), are of importance for 11betaHSD1 activity. We hypothesized that the regulation of hepatic preceptor glucocorticoid metabolism is gender-specific and associated with circulating levels of leptin and TNF-alpha receptors and/or sex hormones.
A total of 34 males and 38 women (14 premenopausal and 22 postmenopausal) underwent physical examination and fasting blood sampling. Insulin sensitivity was tested by euglycemic hyperinsulinemic clamps, and hepatic 11betaHSD1 enzyme activity was estimated by the conversion of orally-ingested cortisone to cortisol.
Hepatic 11betaHSD1 activity was negatively associated with leptin and soluble TNF (sTNF) r1 and sTNFr2 in males. These correlations remained significant after adjustment for age and insulin sensitivity, and for sTNF-alpha receptors also after adjustment of BMI and waist circumference. In contrast, 11beta reduction of cortisone was positively associated to leptin in females after adjustment for BMI and waist circumference.
Hepatic 11beta reduction shows different links to circulating adipocyte-derived hormones in males and females. This emphasizes the need for further studies on tissue-specific regulation of 11betaHSD1 in both genders.
11β-羟基类固醇脱氢酶1型（11βHSD1）介导可的松向皮质醇的转化，它被认为是肥胖相关并发症中的关键酶。实验研究表明，脂肪因子，尤其是瘦素和肿瘤坏死因子-α（TNF-α），对11βHSD1的活性很重要。我们推测，肝脏中糖皮质激素代谢前体的调节具有性别特异性，且与瘦素、TNF-α受体和/或性激素的循环水平有关。
共有34名男性和38名女性（14名绝经前女性和22名绝经后女性）接受了体格检查和空腹采血。通过正常血糖高胰岛素钳夹试验检测胰岛素敏感性，并通过口服可的松向皮质醇的转化来估计肝脏11βHSD1酶的活性。
男性肝脏11βHSD1活性与瘦素、可溶性TNF（sTNF）r1和sTNFr2呈负相关。在调整年龄和胰岛素敏感性后，这些相关性仍然显著，在调整BMI和腰围后，sTNF-α受体的相关性也仍然显著。相比之下，在调整BMI和腰围后，女性可的松的11β还原与瘦素呈正相关。
男性和女性肝脏中可的松的11β还原与循环中脂肪细胞衍生激素的联系不同。这强调了需要进一步研究两性中11βHSD1的组织特异性调节。
