Division of EndocrinologyDepartment of Medical and Surgical Science, Centre for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, University of Bologna, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyEndocrinology UnitQueen's Medical Research Institute, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK
Division of EndocrinologyDepartment of Medical and Surgical Science, Centre for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, University of Bologna, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyEndocrinology UnitQueen's Medical Research Institute, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
Eur J Endocrinol. 2014 Jul;171(1):47-57. doi: 10.1530/EJE-13-1030. Epub 2014 Apr 17.
Abnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has been invoked as a cause of secondary activation of the hypothalamic-pituitary-adrenal axis and hence androgen excess. However, this is based on urinary excretion of cortisol metabolites, which cannot detect tissue-specific changes in metabolism and may be confounded by obesity.
To assess cortisol clearance and whole-body and tissue-specific activities of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) in PCOS.
Case-control study.
Medical center.
A total of 20 overweight-obese unmedicated Caucasian women with PCOS, aged 18-45 years, and 20 Caucasian controls matched for age, BMI, body fat distribution, and HSD11B1 genotypes (rs846910 and rs12086634).
Cortisol metabolites were measured in 24 h urine. During steady-state 9,11,12,12-[(2)H]4-cortisol infusion, cortisol clearance was calculated and whole-body HSD11B1 activity was assessed as the rate of appearance of 9,12,12-(2)H3-cortisol (d3-cortisol). Hepatic HSD11B1 activity was quantified as the generation of plasma cortisol following an oral dose of cortisone. Subcutaneous adipose HSD11B1 activity and HSD11B1 mRNA were measured, ex vivo, in biopsies.
Urinary cortisol metabolite excretion, deuterated cortisol clearance, and the rate of appearance of d3-cortisol did not differ between patients with PCOS and controls. However, hepatic HSD11B1 conversion of oral cortisone to cortisol was impaired (P<0.05), whereas subcutaneous abdominal adipose tissue HSD11B1 mRNA levels and activity were increased (P<0.05) in women with PCOS when compared with controls.
Tissue-specific dysregulation of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased clearance of cortisol may result from obesity rather than PCOS.
多囊卵巢综合征（PCOS）中皮质醇代谢异常被认为是引起下丘脑-垂体-肾上腺轴（HPA）的继发性激活和雄激素过多的原因。然而，这是基于皮质醇代谢产物的尿排泄，它不能检测到代谢的组织特异性变化，并且可能因肥胖而混淆。
评估多囊卵巢综合征（PCOS）中皮质醇清除率以及 11β-羟类固醇脱氢酶 1 型（11β-HSD1（HSD11B1））的全身和组织特异性活性。
病例对照研究。
医疗中心。
共 20 名超重肥胖未经药物治疗的白种人 PCOS 患者，年龄 18-45 岁，20 名白种人对照者年龄、BMI、体脂分布和 HSD11B1 基因型（rs846910 和 rs12086634）相匹配。
24 小时尿中皮质醇代谢产物。在稳态 9、11、12、12-[(2)H]4-皮质醇输注期间，计算皮质醇清除率，并作为 9、12、12-[(2)H3]皮质醇（d3-皮质醇）出现的速率来评估全身 HSD11B1 活性。肝 HSD11B1 活性通过口服考的松后生成的血浆皮质醇来量化。测量活检的皮下脂肪组织 HSD11B1 活性和 HSD11B1mRNA，离体。
PCOS 患者与对照组患者的尿皮质醇代谢产物排泄、氘代皮质醇清除率和 d3-皮质醇出现率无差异。然而，与对照组相比，PCOS 患者口服考的松转化为皮质醇的肝 HSD11B1 转化率受损（P<0.05），而皮下腹部脂肪组织 HSD11B1mRNA 水平和活性增加（P<0.05）。
HSD11B1 的组织特异性失调是 PCOS 的特征，超出了肥胖的范围，而皮质醇清除率的增加可能是由于肥胖而不是 PCOS 引起的。
