Hautanen A, Adlercreutz H
Department of Clinical Chemistry, University of Helsinki, Finland.
J Steroid Biochem Mol Biol. 1996 Apr;58(1):123-33. doi: 10.1016/0960-0760(96)00013-1.
Certain differences in regional fat distribution might be explicable by subtle hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. We examined prospectively PA function relative to abdominal obesity defined by waist-to-hip circumference ratio (WHR) in 71 normotensive men aged 30-55 years. Basal PA activity was assessed by measurements of serum cortisol and plasma corticotropin (ACTH) concentrations during the oral glucose tolerance test (OGTT). Functional activity was examined by dexamethasone suppression and ACTH stimulation tests; responses of 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), cortisol, dehydroepiandrosterone (DHEA), and androstenedione were determined. When the subjects were divided into tertiles for the WHR, the ratio of mean ACTH to mean cortisol during the OGTT was increased (p < 0.05), and the ratio of urinary cortisol to body-mass index was decreased (p < 0.01), whilst the net increments of cortisol (p < 0.05) and 17-OHP (p < 0.05) from 0 to 60 min, as well as the ratio of 17-OHP to S increments (p < 0.05) after ACTH were elevated in the highest vs lowest WHR tertile. The ratio of mean ACTH to mean cortisol (r = 0.495; p < 0.001) during the OGTT, the ratio of net 17-OHP to S increments (r = 0.404; p < 0.001), and the net DHEA (r = 0.276; p = 0.020) and 17-OHP (r = 0.336; p = 0.005) responses to ACTH at 60 min correlated with WHR. In multivariate analyses the ratio of mean ACTH to cortisol, cortisol response to ACTH, and the ratio of net 17-OHP to S increments were all significant predictors of WHR independent of smoking, physical activity, and BMI explaining 49.0% of the variance in WHR. Thus, abdominal obesity may be associated with decreased activity of adrenal 21-hydroxylase. Either obesity-related functional alteration of 21-hydroxylase activity or the high carrier prevalence of genetic defects of this enzyme may explain these findings.
下丘脑 - 垂体 - 肾上腺（HPA）轴的轻微功能亢进可能可以解释区域脂肪分布的某些差异。我们前瞻性地研究了71名年龄在30 - 55岁的血压正常男性中，与通过腰臀围比（WHR）定义的腹部肥胖相关的PA功能。通过口服葡萄糖耐量试验（OGTT）期间测量血清皮质醇和血浆促肾上腺皮质激素（ACTH）浓度来评估基础PA活性。通过地塞米松抑制试验和ACTH刺激试验来检查功能活性；测定17 - 羟孕酮（17 - OHP）、11 - 脱氧皮质醇（S）、皮质醇、脱氢表雄酮（DHEA）和雄烯二酮的反应。当将受试者按WHR分为三分位数时，OGTT期间平均ACTH与平均皮质醇的比值增加（p < 0.05），尿皮质醇与体重指数的比值降低（p < 0.01），而最高WHR三分位数与最低WHR三分位数相比，0至60分钟皮质醇（p < 0.05）和17 - OHP（p < 0.05）的净增量以及ACTH后17 - OHP与S增量的比值（p < 0.05）升高。OGTT期间平均ACTH与平均皮质醇的比值（r = 0.495；p < 0.001）、17 - OHP与S净增量的比值（r = 0.404；p < 0.001）以及60分钟时ACTH刺激后DHEA（r = 0.276；p = 0.020）和17 - OHP（r = 0.336；p = 0.005）的反应与WHR相关。在多变量分析中，平均ACTH与皮质醇的比值、皮质醇对ACTH的反应以及17 - OHP与S净增量的比值均是WHR的显著预测因子，独立于吸烟、身体活动和BMI，可解释WHR变异的49.0%。因此，腹部肥胖可能与肾上腺21 - 羟化酶活性降低有关。21 - 羟化酶活性的肥胖相关功能改变或该酶遗传缺陷的高携带者患病率可能解释这些发现。
