Norbiato G, Bevilacqua M, Vago T, Baldi G, Chebat E, Bertora P, Moroni M, Galli M, Oldenburg N
Servizio di Endocrinologia, Ospedale L. Sacco Vialba, Milan, Italy.
J Clin Endocrinol Metab. 1992 Mar;74(3):608-13. doi: 10.1210/jcem.74.3.1740494.
This study concerns 9 iv drug abusers with acquired immunodeficiency syndrome (AIDS) who developed hypercortisolism without the clinical signs or metabolic consequences of hypercortisolism. All patients were characterized by an Addisonian picture (weakness, weight loss, hypotension, hyponatremia, and intense mucocutaneous melanosis). An acquired form of peripheral resistance to glucocorticoids was suspected. We, therefore, examined glucocorticoid receptor characteristics on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation, which is one of the effects of glucocorticoid receptor activation. Glucocorticoid receptor density was increased in AIDS patients with an Addisonian picture (group 1; 16.2 +/- 9.4 fmol/million cells) compared to values in 12 AIDS patients without an Addisonian picture (group 2; 6.05 +/- 2.6 fmol/million cells; P less than 0.01) and sex- and age-matched controls (3.15 +/- 2.3 fmol/million cells; P less than 0.01). The affinity of glucocorticoid receptors (Kd) was strikingly decreased (9.36 +/- 3.44 nM in group 1; 3.2 +/- 1.5 nM in group 2; 2.0 +/- 0.8 nM in controls; P less than 0.01). [3H]Thymidine incorporation was decreased dose-dependently by dexamethasone in controls and patients; the effect was significantly blunted (P less than 0.05) in group 1 patients, which suggests that activation of glucocorticoid receptor is impaired as a result of the glucocorticoid receptor abnormality. In conclusion, AIDS patients with hypercortisolism and clinical features of peripheral resistance to glucocorticoids are characterized by abnormal glucocorticoid receptors on lymphocytes. Resistance to glucocorticoids implies a complex change in immune-endocrine function, which may be important in the course of immunodeficiency syndrome.
本研究涉及9名患有获得性免疫缺陷综合征（AIDS）的静脉注射毒品使用者，他们出现了皮质醇增多症，但无皮质醇增多症的临床体征或代谢后果。所有患者均表现为艾迪生病貌（虚弱、体重减轻、低血压、低钠血症和严重的黏膜皮肤黑色素沉着）。怀疑存在一种后天获得性的外周对糖皮质激素抵抗形式。因此，我们通过测量[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（这是糖皮质激素受体激活的效应之一），来检测单核白细胞上的糖皮质激素受体特性。与12名无艾迪生病貌的AIDS患者（第2组；6.05±2.6 fmol/百万细胞）以及性别和年龄匹配的对照组（3.15±2.3 fmol/百万细胞）相比，有艾迪生病貌的AIDS患者（第1组；16.2±9.4 fmol/百万细胞）的糖皮质激素受体密度增加（P＜0.01）。糖皮质激素受体的亲和力（解离常数Kd）显著降低（第1组为9.36±3.44 nM；第2组为3.2±1.5 nM；对照组为2.0±0.8 nM；P＜0.01）。地塞米松可使对照组和患者的[3H]胸腺嘧啶核苷掺入呈剂量依赖性减少；第1组患者的这种效应明显减弱（P＜0.05），这表明由于糖皮质激素受体异常，糖皮质激素受体的激活受到损害。总之，患有皮质醇增多症且具有外周对糖皮质激素抵抗临床特征的AIDS患者，其淋巴细胞上的糖皮质激素受体异常。对糖皮质激素的抵抗意味着免疫 - 内分泌功能的复杂变化，这在免疫缺陷综合征的病程中可能很重要。
