Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):127-32. doi: 10.1016/j.jsbmb.2010.12.002. Epub 2010 Dec 13.
Polycystic ovary syndrome (PCOS) is characterized by insulin resistance (IR) and central obesity. The impact of adipose tissue cortisol reactivation by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on markers of obesity and IR was assessed in PCOS patients. Eighty-five PCOS patients and 43 controls were enrolled for subcutaneous adipose tissue biopsy; 25/85 patients and 29/43 controls underwent also visceral adipose tissue biopsy. HSD11B1 gene expression and expression of lipid metabolism genes were measured in subcutaneous and visceral adipose tissues. Anthropometric and biochemical markers of IR and PCOS were also assessed. HSD11B1 expression in visceral and subcutaneous adipose tissue was increased in PCOS patients compared to controls (p<0.05). After BMI adjustment, the difference was no longer significant. In PCOS patients, visceral HSD11B1 expression correlated positively with waist circumference (p=0.001), BMI (p=0.002), plasma insulin (p<0.05), systolic blood pressure (p=0.003), and lipoprotein lipase (LPL), hormone-sensitive lipase (LIPE) and peroxisome-proliferator activated receptor γ gene expression. Subcutaneous HSD11B1 expression correlated positively with BMI, waist circumference (p<0.001 for both) and HOMA-IR (p=0.003), and negatively with LPL, LIPE, adiponectin and glucose transporter GLUT4 gene expression. HSD11B1 expression in both depots showed a negative correlation with plasma HDL-cholesterol (p<0.03) and a positive one with C-reactive protein (p<0.001). In multiple regression analysis, HSD11B1 expression in visceral adipose tissue was most prominently associated with waist circumference, and that in subcutaneous adipose tissue with BMI (p<0.001 for both). Our results show that PCOS is not associated with increased HSD11B1 expression once adiposity is controlled for. Increased expression of this gene correlates with markers of adiposity and predicts IR and an unfavorable metabolic profile, independently of PCOS.
多囊卵巢综合征（PCOS）的特征是胰岛素抵抗（IR）和中心性肥胖。本研究评估了 11β-羟类固醇脱氢酶 1（11β-HSD1）对脂肪组织皮质醇再激活对肥胖和 IR 标志物的影响。85 例 PCOS 患者和 43 例对照者接受了皮下脂肪组织活检；25/85 例患者和 29/43 例对照者还接受了内脏脂肪组织活检。测量了皮下和内脏脂肪组织中 HSD11B1 基因表达和脂质代谢基因的表达。还评估了 IR 和 PCOS 的人体测量学和生化标志物。与对照组相比，PCOS 患者的内脏和皮下脂肪组织中的 HSD11B1 表达增加（p<0.05）。在调整 BMI 后，差异不再显著。在 PCOS 患者中，内脏 HSD11B1 表达与腰围（p=0.001）、BMI（p=0.002）、血浆胰岛素（p<0.05）、收缩压（p=0.003）和脂蛋白脂肪酶（LPL）、激素敏感脂肪酶（LIPE）和过氧化物酶体增殖物激活受体γ基因表达呈正相关。皮下 HSD11B1 表达与 BMI、腰围（两者均为 p<0.001）和 HOMA-IR（p=0.003）呈正相关，与 LPL、LIPE、脂联素和葡萄糖转运蛋白 GLUT4 基因表达呈负相关。两部位的 HSD11B1 表达与血浆高密度脂蛋白胆固醇呈负相关（p<0.03），与 C 反应蛋白呈正相关（p<0.001）。多元回归分析显示，内脏脂肪组织中 HSD11B1 的表达与腰围最为显著相关，而皮下脂肪组织中 HSD11B1 的表达与 BMI 最显著相关（两者均为 p<0.001）。我们的结果表明，一旦控制肥胖，PCOS 与 HSD11B1 表达增加无关。该基因的表达增加与肥胖标志物相关，并可预测 IR 和不良的代谢谱，与 PCOS 无关。
