Invitti C, Redaelli G, Baldi G, Cavagnini F
2nd Chair of Endocrinology, University of Milan, Istituto Scientifico Ospedale San Luca, Italy.
Biol Psychiatry. 1999 Jun 1;45(11):1467-71. doi: 10.1016/s0006-3223(98)00189-9.
Patients with anorexia nervosa do not display cushingoid features in spite of elevated cortisol plasma levels. Whether a cortisol resistance or a reduced availability of the metabolic substrates necessary to develop the effect of glucocorticoids is responsible for this has not been established.
Twenty-two patients with severe restrictive anorexia nervosa, 10 patients with active Cushing's disease, and 24 healthy volunteers without psychiatric disorders or mood alterations were investigated. Glucocorticoid receptor characteristics were examined on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation, which represents an index of DNA synthesis.
The number of glucocorticoid receptors on mononuclear leukocytes (MNL) was comparable in patients with anorexia nervosa, patients with active Cushing's disease, and normal subjects (binding capacity 3.3 +/- 0.23 vs. 3.7 +/- 0.30 and 3.5 +/- 0.20 fmol/10(6) cells). Conversely, glucocorticoid receptor affinity was significantly decreased in anorexia nervosa as well as in Cushing's patients compared to control subjects (dissociation constant 4.0 +/- 0.31 and 4.1 +/- 0.34 vs. 2.9 +/- 0.29 nmol/L, p < .001) and inversely correlated with the levels of urinary free cortisol in both groups of patients. Basal [3H]thymidine incorporation in MNL was significantly reduced in anorexia nervosa as well as in Cushing's patients compared to control subjects (p < .001) and was diminished by dexamethasone to an extent similar to control subjects in patients with anorexia nervosa, but significantly (p < .001) less in those with Cushing's disease. In patients with anorexia nervosa, the incorporation of [3H]thymidine into the MNL was inversely correlated with urinary free cortisol levels.
These data indicate that the lack of cushingoid features in patients with anorexia nervosa is not ascribable to a reduced sensitivity to glucocorticoids but is more likely due to the paucity of metabolic substrates.
尽管神经性厌食症患者血浆皮质醇水平升高,但他们并未表现出库欣样特征。目前尚未确定这是由于皮质醇抵抗还是缺乏发挥糖皮质激素作用所需的代谢底物所致。
对22例严重限制性神经性厌食症患者、10例活动性库欣病患者和24名无精神疾病或情绪改变的健康志愿者进行了研究。通过测量[3H]地塞米松结合以及地塞米松对[3H]胸腺嘧啶核苷掺入的影响(这代表DNA合成指标),在单核细胞上检测糖皮质激素受体特征。
神经性厌食症患者、活动性库欣病患者和正常受试者单核细胞(MNL)上糖皮质激素受体的数量相当(结合能力分别为3.3±0.23、3.7±0.30和3.5±0.20 fmol/10(6)细胞)。相反,与对照组相比,神经性厌食症患者和库欣病患者的糖皮质激素受体亲和力显著降低(解离常数分别为4.0±0.31和4.1±0.34,而对照组为2.9±0.29 nmol/L,p <.001),并且在两组患者中均与尿游离皮质醇水平呈负相关。与对照组相比,神经性厌食症患者和库欣病患者MNL中基础[3H]胸腺嘧啶核苷掺入显著减少(p <.001),并且地塞米松使其减少的程度在神经性厌食症患者中与对照组相似,但在库欣病患者中显著减少(p <.001)。在神经性厌食症患者中,[3H]胸腺嘧啶核苷掺入MNL与尿游离皮质醇水平呈负相关。
这些数据表明,神经性厌食症患者缺乏库欣样特征并非归因于对糖皮质激素的敏感性降低,而更可能是由于代谢底物不足。