Reduced glucocorticoid receptor α expression in mood disorder patients and first-degree relatives

Reduced glucocorticoid receptor α expression in mood disorder patients and first-degree relatives
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DOI:
10.1016/j.biopsych.2005.09.026
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发表时间:
2006-04-15
影响因子:
10.6
通讯作者:
Watanabe, Y
Watanabe, Y
中科院分区:
医学1区
文献类型:
--
作者:
Matsubara, T;Funato, H;Watanabe, Y

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背景:患有情绪障碍的个体在应激反应中表现出下丘脑-垂体-肾上腺(HPA)轴功能的改变。糖皮质激素受体(GR)在HPA轴的负反馈调节中起重要作用。GR α和GR β两种蛋白异构体具有不同的生物活性,但情绪障碍患者外周血细胞中GR α信使RNA (mMNA)和GR β mRNA的表达是否发生改变尚不清楚。方法:采用定量反转录聚合酶链法。测定重性抑郁症患者(抑郁症患者18例,缓解性患者38例)、双相情感障碍患者(抑郁症患者13例,缓解性患者35例)、正常对照(31例)、一级亲属双相情感障碍患者17例、双相情感障碍患者15例外周血细胞的RT-PCR反应(RT-PCR)、GR α mRNA和GRP mRNA。结果:双相抑郁和重度抑郁患者在当前抑郁状态和缓解期均表现出GR α mRNA的表达降低。双相情感障碍患者一级亲属GR α mRNA表达减少,情绪障碍患者未见GR β mRNA表达改变。结论:我们的研究结果表明GR α mRNA表达的减少可能是性状依赖的,并与情绪障碍的病理生理有关。
Background: Individuals with mood disorders exhibit altered function of the hypothalamic-pituitiary-adrenal (HPA) axis in response to stress. The glucocorticoid receptor (GR) plays an important role in the negative feedback regulation of The HPA axis. There are two protein isoforms of GR GR alpha and GR beta which have distinct biological activity, It has not been examined whether GR alpha messenger RNA (mMNA) and GR beta mRNA expressions are altered in peripheral blood cells of mood disorder patients.Methods: Using quantitative reverse transcription polymerase chain. reaction (RT-PCR), GR alpha mRNA and GRP mRNA were measured in peripheral blood cells of major depressive disorder patients (depressive n = 18; remissive n = 38), bipolar disorder patients (depressive n = 13, remissive n = 35), normal control subjects (n = 31), and first-degree relatives bipolar depressive (n = 17) and bipolar (n = 15) disorder patients.Results: Reduced expression of GR alpha mRNA was shown in both bipolar and major depressive disorderpatients in a current depressive state as well as in remission. First-degree relatives of bipolar disorderpatients also showed GR alpha mRNA reduction, Altered GR beta mRNA expression was not found in mood disorder patients.Conclusions: Our results suggest that reduced GR alpha mRNA expression might be trait-dependent and associated with the pathophysiology of mood disorders.