University of Belgrade, Institute for Biological Research Siniša Stanković, Department of Biochemistry, Belgrade, Serbia.
Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jun 3;43:238-45. doi: 10.1016/j.pnpbp.2013.01.005. Epub 2013 Jan 16.
Posttraumatic stress disorder (PTSD) has been shown to be associated with altered glucocorticoid receptor (GR) activity. We studied the expression and functional properties of the receptor in peripheral blood mononuclear cells (PBMCs) from non-traumatized healthy individuals (healthy controls; n=85), and war trauma-exposed individuals with current PTSD (n=113), with life-time PTSD (n=61) and without PTSD (trauma controls; n=88). The aim of the study was to distinguish the receptor alterations related to PTSD from those related to trauma itself or to resilience to PTSD.
Functional status of the receptor was assessed by radioligand binding and lysozyme synthesis inhibition assays. The level of GR gene expression was measured by quantitative PCR and immunoblotting.
Current PTSD patients had the lowest, while trauma controls had the highest number of glucocorticoid binding sites (Bmax) in PBMCs. Hormone-binding potential (Bmax/KD ratio) of the receptor was diminished in the current PTSD group in comparison to all other study groups. Correlation between Bmax and KD that normally exists in healthy individuals was decreased in the current PTSD group. Contrasting Bmax data, GR protein level was lower in trauma controls than in participants with current or life-time PTSD.
Current PTSD is characterized by reduced lymphocyte GR hormone-binding potential and by disturbed compensation between Bmax and hormone-binding affinity. Resilience to PTSD is associated with enlarged fraction of the receptor molecules capable of hormone binding, within the total receptor molecule population in PBMCs.
创伤后应激障碍(PTSD)与糖皮质激素受体(GR)活性改变有关。我们研究了未受创伤的健康个体(健康对照组;n=85)和创伤后应激障碍(PTSD)患者(n=113)、终生 PTSD 患者(n=61)和无 PTSD 患者(创伤对照组;n=88)外周血单个核细胞(PBMC)中受体的表达和功能特性。本研究的目的是区分与 PTSD 相关的受体改变与与创伤本身或对 PTSD 的适应能力相关的改变。
通过放射性配体结合和溶菌酶合成抑制试验评估受体的功能状态。通过定量 PCR 和免疫印迹测量 GR 基因表达水平。
当前 PTSD 患者的 PBMC 中糖皮质激素结合位点(Bmax)数量最低,而创伤对照组最高。与所有其他研究组相比,当前 PTSD 组的受体激素结合潜力(Bmax/KD 比值)降低。在健康个体中通常存在的 Bmax 和 KD 之间的相关性在当前 PTSD 组中降低。与 Bmax 数据相反,创伤对照组的 GR 蛋白水平低于当前或终生 PTSD 患者。
当前 PTSD 的特征是淋巴细胞 GR 激素结合潜力降低,Bmax 和激素结合亲和力之间的代偿失调。对 PTSD 的适应能力与 PBMC 中总受体分子群体中能够结合激素的受体分子的较大部分有关。