Sex differences in stress-related receptors: ″micro″ differences with ″macro″ implications for mood and anxiety disorders.
Sex differences in stress-related receptors: ″micro″ differences with ″macro″ implications for mood and anxiety disorders.
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DOI：
10.1186/2042-6410-4-2
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发表时间：
2013-01-21
影响因子：
7.9
通讯作者：
Bangasser DA
中科院分区：
文献类型：
--
作者：
Bangasser DA
与压力有关的精神障碍，如单相抑郁症和创伤后应激障碍（PTSD），在女性中比男性更常见。新的研究表明，应激激素、促肾上腺皮质激素释放因子（CRF）和糖皮质激素受体的性别差异导致了这种差异。例如，大鼠杏仁核中CRF受体结合的性别差异可能使雌性大鼠在应激事件后更容易焦虑。此外，CRF受体信号传导和蓝斑唤醒中心运输的性别差异结合联合收割机使女性对低水平的CRF更敏感，对高水平的CRF适应性较差。女性的这些受体差异可能导致过度觉醒，这是一种与抑郁症和创伤后应激障碍症状相关的失调状态。与CRF受体中观察到的性别差异相似，糖皮质激素受体（GR）功能的性别差异似乎也使女性在应激事件后更容易发生失调。在下丘脑垂体肾上腺轴激活后，GR对抑制额外糖皮质激素释放的负反馈过程至关重要。与雄性大鼠相比，雌性大鼠在慢性青春期应激后具有较少的GR和受损的GR易位，其影响与较慢的糖皮质激素负反馈有关。因此，在慢性压力的条件下，女性减弱的负反馈会导致高皮质醇血症，这是一种被认为会导致抑郁的内分泌状态。总之，这些研究表明，压力相关受体的性别差异使女性更容易进入压力反应失调状态，与情绪和焦虑症的发展有关。这些受体的性别差异的发展，新的药物治疗的影响也进行了讨论。
Stress-related psychiatric disorders, such as unipolar depression and post-traumatic stress disorder (PTSD), occur more frequently in women than in men. Emerging research suggests that sex differences in receptors for the stress hormones, corticotropin releasing factor (CRF) and glucocorticoids, contribute to this disparity. For example, sex differences in CRF receptor binding in the amygdala of rats may predispose females to greater anxiety following stressful events. Additionally, sex differences in CRF receptor signaling and trafficking in the locus coeruleus arousal center combine to make females more sensitive to low levels of CRF, and less adaptable to high levels. These receptor differences in females could lead to hyperarousal, a dysregulated state associated with symptoms of depression and PTSD. Similar to the sex differences observed in CRF receptors, sex differences in glucocorticoid receptor (GR) function also appear to make females more susceptible to dysregulation after a stressful event. Following hypothalamic pituitary adrenal axis activation, GRs are critical to the negative feedback process that inhibits additional glucocorticoid release. Compared to males, female rats have fewer GRs and impaired GR translocation following chronic adolescent stress, effects linked to slower glucocorticoid negative feedback. Thus, under conditions of chronic stress, attenuated negative feedback in females would result in hypercortisolemia, an endocrine state thought to cause depression. Together, these studies suggest that sex differences in stress-related receptors shift females more easily into a dysregulated state of stress reactivity, linked to the development of mood and anxiety disorders. The implications of these receptor sex differences for the development of novel pharmacotherapies are also discussed.