The putative estrogen receptor GPER1 (the former orphan receptor GPR30) is discussed to be involved in emotional and cognitive functions and stress control. We recently described the induction of anxiety-like effects by the GPER1 agonist G-1 upon systemic injection into mice. To contribute to a better understanding of the role of GPER1 in anxiety and stress, we investigated germ-line GPER1 deficient mice. Our experiments revealed marked differences between the sexes. A mild but consistent phenotype of increased exploratory drive was observed in the home cage, the elevated plus maze and the light-dark choice test in male GPER1 KO mice. In contrast, female GPER1-KO mice displayed a less pronounced phenotype in these tests. Estrous-stage dependent mild anxiolytic-like effects were observed solely in the open field test. Notably, we observed a strong shift in acute stress coping behavior in the tail suspension test and basal corticosterone levels in different phases of the estrous cycle in female GPER1-KO mice. Our data, in line with previous reports, suggest that GPER1 is involved in anxiety and stress control. Surprisingly, its effects appear to be stronger in male than female mice.

中文翻译：

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GPER1 (GPR30) 基因敲除小鼠以性别和范式依赖的方式表现出焦虑减少和压力反应改变。

推定的雌激素受体 GPER1（前孤儿受体 GPR30）被讨论为参与情绪和认知功能以及压力控制。我们最近描述了 GPER1 激动剂 G-1 在全身注射到小鼠后诱导的焦虑样作用。为了更好地理解 GPER1 在焦虑和压力中的作用，我们研究了生殖系 GPER1 缺陷小鼠。我们的实验揭示了两性之间的显着差异。在雄性 GPER1 KO 小鼠的家笼、高架十字迷宫和明暗选择测试中观察到了一种温和但一致的探索性驱动表型增加。相比之下，雌性 GPER1-KO 小鼠在这些测试中表现出不太明显的表型。仅在旷场试验中观察到发情期依赖的轻度抗焦虑样作用。尤其，我们观察到在雌性 GPER1-KO 小鼠的发情周期的不同阶段，在尾悬垂试验中急性应激应对行为和基础皮质酮水平发生了强烈变化。我们的数据与之前的报告一致，表明 GPER1 参与焦虑和压力控制。令人惊讶的是，它对雄性小鼠的影响似乎比雌性小鼠强。