Chrousos G P, Detera-Wadleigh S D, Karl M
NIH, Bethesda, MD 20892.
Ann Intern Med. 1993 Dec 1;119(11):1113-24. doi: 10.7326/0003-4819-119-11-199312010-00009.
Glucocorticoid resistance results from the partial, albeit apparently generalized, inability of glucocorticoids to exert their effects on target tissues. The condition is associated with compensatory increases in circulating pituitary corticotropin and cortisol, with the former causing excess secretion of both adrenal androgens and adrenal steroid biosynthesis intermediates with salt-retaining activity. The manifestations of glucocorticoid resistance vary from chronic fatigue (perhaps a result of glucocorticoid deficiency in the central nervous system) to various degrees of hypertension with or without hypokalemic alkalosis or hyperandrogenism, or both, caused by increased cortisol and other salt-retaining steroids and adrenal androgens, respectively. In women, hyperandrogenism can result in acne, hirsutism, menstrual irregularities, oligoanovulation, and infertility; in men, it may lead to infertility and in children, to precocious puberty. Different molecular defects, such as point mutations or a microdeletion of the highly conserved glucocorticoid receptor gene, alter the functional characteristics or concentrations of the intracellular receptor and appear to cause glucocorticoid resistance. The extreme variability in the clinical manifestations of glucocorticoid resistance and its mimicry of many common diseases can be explained by the overall degree of glucocorticoid resistance, differing sensitivity of target tissues to mineralocorticoids or androgens or both, and perhaps different biochemical defects of the glucocorticoid receptor, with selective resistance of certain glucocorticoid responses in specific tissues. The various different symptoms of classic glucocorticoid resistance and the theoretical potential of this condition to appear surreptitiously emphasize the importance of the glucocorticoid receptor in the pathogenesis of human disease.
糖皮质激素抵抗是指糖皮质激素对靶组织发挥作用的能力部分丧失，尽管这种丧失显然具有全身性。该病症与循环垂体促肾上腺皮质激素和皮质醇的代偿性增加有关，前者会导致肾上腺雄激素和具有保盐活性的肾上腺类固醇生物合成中间体分泌过多。糖皮质激素抵抗的表现各不相同，从慢性疲劳（可能是中枢神经系统糖皮质激素缺乏的结果）到不同程度的高血压，伴有或不伴有低钾性碱中毒或高雄激素血症，或两者皆有，分别由皮质醇和其他保盐类固醇以及肾上腺雄激素增加所致。在女性中，高雄激素血症可导致痤疮、多毛症、月经不调、排卵稀少和不孕；在男性中，可能导致不育，在儿童中，则会导致性早熟。不同的分子缺陷，如高度保守的糖皮质激素受体基因的点突变或微缺失，会改变细胞内受体的功能特性或浓度，似乎导致了糖皮质激素抵抗。糖皮质激素抵抗临床表现的极端变异性及其对许多常见疾病的模仿，可通过糖皮质激素抵抗的总体程度、靶组织对盐皮质激素或雄激素或两者的不同敏感性，以及可能的糖皮质激素受体不同生化缺陷来解释，某些组织中存在对特定糖皮质激素反应的选择性抵抗。经典糖皮质激素抵抗的各种不同症状以及这种病症可能隐匿出现的理论可能性，强调了糖皮质激素受体在人类疾病发病机制中的重要性。
