The glucocorticoid receptor: part of the solution or part of the problem?
The glucocorticoid receptor: part of the solution or part of the problem?
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DOI：
10.1177/1359786806066063
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发表时间：
2006-07-01
期刊：
影响因子：
--
通讯作者：
Pariante, Carmine M
中科院分区：
文献类型：
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作者：
Pariante, Carmine M
临床研究表明，由于糖皮质激素受体（GR）介导的负反馈（糖皮质激素抵抗）受损，重度抑郁症患者的下丘脑-垂体-肾上腺（HPA）轴过度活跃和皮质醇水平升高。此外，临床和实验研究表明，抗抑郁药增加GR功能，从而导致糖皮质激素抵抗的解决。有趣的是，许多研究也表明，用激动剂和拮抗剂操纵GR功能具有抗抑郁作用，事实上，其他针对HPA轴和皮质醇分泌的药物-甚至对HPA轴具有相反作用的药物-也具有抗抑郁作用。这些研究并不支持皮质醇对大脑有“负面”影响的观点。相反，这篇论文的结论是，由于糖皮质激素抵抗，皮质醇对大脑的“积极”作用缺乏，这可能与抑郁症的发病机制有关。
Clinical studies have demonstrated hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and increased levels of cortisol in patients with major depression, because of an impairment of glucocorticoid receptor (GR)-mediated negative feedback (glucocorticoid resistance). Moreover, clinical and experimental studies have shown that antidepressants increase GR function, thus leading to resolution of glucocorticoid resistance. Interestingly, a number of studies have also demonstrated that manipulating GR function with both agonists and antagonists has an antidepressant effect, and indeed that other drugs targeting the HPA axis and cortisol secretion - even drugs with opposite effects on the HPA axis - have antidepressant effects. These studies do not support the notion that cortisol has 'negative' effects on the brain. On the contrary, this paper concludes that a lack of the 'positive' effects of cortisol on the brain, because of glucocorticoid resistance, is likely to be involved in the pathogenesis of depression.