Sex differences in the traumatic stress response: the role of adult gonadal hormones.
Sex differences in the traumatic stress response: the role of adult gonadal hormones.
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DOI：
10.1186/s13293-018-0192-8
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发表时间：
2018-07-13
影响因子：
7.9
通讯作者：
Jordan CL
中科院分区：
文献类型：
--
作者：
Pooley AE;Benjamin RC;Sreedhar S;Eagle AL;Robison AJ;Mazei-Robison MS;Breedlove SM;Jordan CL
我们以前的研究表明，成年雌性大鼠对创伤的反应与成年雄性大鼠不同，概括了女性和男性表现出的创伤后应激障碍（PTSD）症状的性别差异。在这里，我们提出了两个问题：女性表型取决于（1）社会住房条件和/或（2）循环性腺激素？在第一项研究中，比较了单独或成对饲养的雌性动物的单次长期应激（SPS）的影响。对于第二项研究，成年雄性和雌性大鼠在暴露于SPS前2周进行性腺切除或假性腺切除，其中一半的性腺切除大鼠给予睾酮。除了大鼠创伤反应的典型测量，声惊吓反应（ASR）和地塞米松抑制试验（DST）外，我们还使用了其他两种通常用于评估抑郁样反应的测量方法，即社会互动和蔗糖偏好。还检测了下丘脑中糖皮质激素受体（GR）的表达。我们现在报告说，不同的创伤反应的雌性大鼠是不受社会住房条件。此外，在本研究中复制的基于ASR和DST的对SPS的反应的性别差异独立于成年性腺激素。无论激素状态，创伤男性表现出高反应表型，而创伤女性没有。此外，成年期的睾酮治疗并没有使女性对创伤的反应男性化。值得注意的是，蔗糖偏好和社会互动测试显示，创伤的影响，女性，但不是在男性，与SPS蔗糖偏好依赖于卵巢激素的影响。SPS对雌性下丘脑GR表达的影响也依赖于性腺激素。我们建议，雌性大鼠的创伤反应是抑郁的性质，概括的女性偏见PTSD的内化症状和严重抑郁症的外化症状的男性相比。PTSD的假定核心标志物（增强的ASR和皮质酮的负反馈控制）显然只与男性相关，并且独立于成人性腺激素。这种创伤反应的性别差异可能在生命的早期就决定了。我们的结论是，男性和女性表现出根本不同的反应创伤，不简单地反映了弹性的差异。本文的在线版本（10.1186/s13293-018-0192-8）包含补充材料，可供授权用户使用。
Our previous study revealed that adult female rats respond differently to trauma than adult males, recapitulating sex differences in symptoms of post-traumatic stress disorder (PTSD) exhibited by women and men. Here, we asked two questions: does the female phenotype depend on (1) social housing condition and/or (2) circulating gonadal hormones? For the first study, the effects of single prolonged stress (SPS) were compared for females singly or pair-housed. For the second study, adult male and female rats were gonadectomized or sham-gonadectomized 2 weeks prior to exposure to SPS, with half the gonadectomized rats given testosterone. In addition to the typical measures of the trauma response in rats, acoustic startle response (ASR), and the dexamethasone suppression test (DST), we also used two other measures typically used to assess depressive-like responses, social interaction and sucrose preference. Glucocorticoid receptor (GR) expression in the hypothalamus was also examined. We now report that the distinct trauma response of female rats is not influenced by social housing condition. Moreover, sex differences in the response to SPS based on ASR and DST, replicated in the current study, are independent of adult gonadal hormones. Regardless of hormonal status, traumatized males show a hyper-responsive phenotype whereas traumatized females do not. Moreover, testosterone treatment in adulthood did not masculinize the response to trauma in females. Notably, both sucrose preference and social interaction tests revealed an effect of trauma in females but not in males, with the effects of SPS on sucrose preference dependent on ovarian hormones. Effects of SPS on GR expression in the hypothalamus also depended on gonadal hormones in females. We propose that the trauma response for female rats is depressive in nature, recapitulating the female bias in PTSD for internalizing symptoms and major depression in contrast to the externalizing symptoms of males. Presumed core markers of PTSD (enhanced ASR and negative feedback control of corticosterone) are apparently relevant only to males and are independent of adult gonadal hormones. Such sex differences in trauma responding are likely determined earlier in life. We conclude that males and females show fundamentally different responses to trauma that do not simply reflect differences in resilience. The online version of this article (10.1186/s13293-018-0192-8) contains supplementary material, which is available to authorized users.
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