Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans.
Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans.
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作者：
Stimson RH;Andersson J;Andrew R;Redhead DN;Karpe F;Hayes PC;Olsson T;Walker BR
目的11羟基类固醇脱氢酶1(11β-β-HSD1)能从皮质醇中再生皮质醇。11例肥胖患者皮下脂肪组织中β-HSD1mRNA和活性在体外均升高。抑制11β-HSD1是治疗2型糖尿病的一种有前景的方法。然而，11β-HSD1从脂肪组织中释放的皮质醇及其对门静脉皮质醇浓度的影响尚未在体内得到定量。研究设计和方法-6名健康男性接受了9，11，12，12-[2H]4-皮质醇注射，同时采集了动脉化和腹壁浅静脉血样。4名稳定的慢性肝病患者和原位经颈静脉肝内门体分流术的患者同时从门静脉、肝静脉和动脉化的外周静脉输注示踪剂。结果皮下脂肪组织有显著的皮质醇和9，12，12-[2H]3-皮质醇释放(分别为15.0[95%CI 0.4~29.5]和8.7[0.2~17.2]pmol.min−1·100g−1脂肪组织)。内脏皮质醇和9，12，12-[2H]3-皮质醇的释放(分别为13.5[3.6-23.5]和8.0[2.6-13.5]nmol/min)全部由肝脏释放，未检测到皮质醇从内脏组织释放到门静脉。结论：人类皮下脂肪组织通过11β-HSD1释放皮质醇，肥胖时酶表达增加可能增加局部糖皮质激素信号，促进全身皮质醇再生。然而，内脏脂肪11β-HSD1活性不足以增加门静脉皮质醇浓度，从而影响肝内糖皮质激素信号转导。
OBJECTIVE—11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates cortisol from cortisone. 11β-HSD1 mRNA and activity are increased in vitro in subcutaneous adipose tissue from obese patients. Inhibition of 11β-HSD1 is a promising therapeutic approach in type 2 diabetes. However, release of cortisol by 11β-HSD1 from adipose tissue and its effect on portal vein cortisol concentrations have not been quantified in vivo. RESEARCH DESIGN AND METHODS—Six healthy men underwent 9,11,12,12-[2H]4-cortisol infusions with simultaneous sampling of arterialized and superficial epigastric vein blood sampling. Four men with stable chronic liver disease and a transjugular intrahepatic porto-systemic shunt in situ underwent tracer infusion with simultaneous sampling from the portal vein, hepatic vein, and an arterialized peripheral vein. RESULTS—Significant cortisol and 9,12,12-[2H]3-cortisol release were observed from subcutaneous adipose tissue (15.0 [95% CI 0.4–29.5] and 8.7 [0.2–17.2] pmol · min−1 · 100 g−1 adipose tissue, respectively). Splanchnic release of cortisol and 9,12,12-[2H]3-cortisol (13.5 [3.6–23.5] and 8.0 [2.6–13.5] nmol/min, respectively) was accounted for entirely by the liver; release of cortisol from visceral tissues into portal vein was not detected. CONCLUSIONS—Cortisol is released from subcutaneous adipose tissue by 11β-HSD1 in humans, and increased enzyme expression in obesity is likely to increase local glucocorticoid signaling and contribute to whole-body cortisol regeneration. However, visceral adipose 11β-HSD1 activity is insufficient to increase portal vein cortisol concentrations and hence to influence intrahepatic glucocorticoid signaling.