Ample evidence suggests that estrogens have strong influences on the occurrence of stress-related mood disorders, but the underlying mechanisms remain poorly understood. Through multiple approaches, we demonstrate that the G protein-coupled estrogen receptor (GPER) is widely distributed along the HPA axis and in brain structures critically involved in mood control. Genetic ablation of GPER in the rat resulted in significantly lower basal serum corticosterone level but enhanced ACTH release in response to acute restraint stress, especially in the female. GPER^-/- rats of either sex displayed increased anxiety-like behaviors and deficits in learning and memory. Additionally, GPER deficiency led to aggravation of anxiety-like behaviors following single-prolonged stress (SPS). SPS caused significant decreases in serum corticosterone in WT but not in GPER-deficient rats. The results highlight an important role of GPER at multiple sites in regulation of the HPA axis and mood.

中文翻译：

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GPER 缺陷大鼠表现出较低的血清皮质酮水平和增加的焦虑样行为。

大量证据表明，雌激素对压力相关情绪障碍的发生有很大影响，但其潜在机制仍知之甚少。通过多种方法，我们证明 G 蛋白偶联雌激素受体 (GPER) 广泛分布在 HPA 轴和与情绪控制密切相关的大脑结构中。大鼠 GPER 的遗传消融导致基础血清皮质酮水平显着降低，但响应急性束缚应激的 ACTH 释放增加，尤其是在雌性中。GPER ^-/-任何一种性别的老鼠都表现出更多的焦虑样行为以及学习和记忆方面的缺陷。此外，GPER 缺乏导致单长期压力 (SPS) 后焦虑样行为的加重。SPS 导致 WT 中血清皮质酮的显着降低，但在 GPER 缺陷大鼠中没有。结果突出了 GPER 在多个位点在调节 HPA 轴和情绪方面的重要作用。