Arai K, Chrousos G P
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Steroids. 1995 Jan;60(1):173-9. doi: 10.1016/0039-128x(94)00007-y.
Glucocorticoid resistance results from incomplete but apparently generalized inability of glucocorticoids to exert their effects on their target tissues. The condition is associated with compensatory elevation of circulating ACTH 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 asymptomatic to different degrees of hypertension and/or hypokalemic alkalosis and/or hyperandrogenism, caused by elevation cortisol and other salt-retaining steroids, and of adrenal androgens, respectively. In women, hyperandrogenism can result in acne, hirsutism, male type baldness, 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 microdeletions of the highly conserved glucocorticoid receptor gene, alter the functional characteristics or concentrations of the intracellular receptor and cause glucocorticoid resistance. The extreme variability in the clinical manifestations of glucocorticoid resistance and its mimicry of many common diseases can be explained by different degrees of glucocorticoid resistance, differing sensitivity of target tissues to mineralocorticoids and/or androgens or both, and perhaps different biochemical defects of the glucocorticoid receptor. Mineralocorticoid resistance results from the inability of aldosterone to exert its effect on target tissues. The syndrome is associated with salt loss, hypotension, and hyperkalemic acidosis. We have cloned and sequenced the cDNA of five unrelated patients with this syndrome and have not found any mutations of pathophysiological significance that would explain the resistance of these patients to aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
糖皮质激素抵抗是由于糖皮质激素对其靶组织发挥作用的能力不完全但显然普遍受损所致。该病症与循环中促肾上腺皮质激素（ACTH）和皮质醇的代偿性升高有关，前者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，从无症状到因皮质醇和其他保盐类固醇升高分别导致不同程度的高血压和/或低钾性碱中毒和/或高雄激素血症。在女性中，高雄激素血症可导致痤疮、多毛症、男性型秃发、月经不规律、排卵稀少和不孕；在男性中，可能导致不育；在儿童中则导致性早熟。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，从而导致糖皮质激素抵抗。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由不同程度的糖皮质激素抵抗、靶组织对盐皮质激素和/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。盐皮质激素抵抗是由于醛固酮无法对靶组织发挥作用所致。该综合征与失盐、低血压和高钾性酸中毒有关。我们已对五名患有该综合征的无关患者的cDNA进行了克隆和测序，未发现任何具有病理生理学意义的突变可解释这些患者对醛固酮的抵抗。（摘要截于250字）
