Estradiol, the most potent and prevalent member of the estrogen class of steroid hormones and is expressed in both sexes. Functioning as a neuroactive steroid, it plays a crucial role in modulating neurotransmitter systems affecting neuronal circuits and brain functions including learning and memory, reward and sexual behaviors. These neurotransmitter systems encompass the serotonergic, dopaminergic, and glutamatergic signaling pathways. Consequently, this review examines the pivotal role of estradiol and its receptors in the regulation of these neurotransmitter systems in the brain. Through a comprehensive analysis of current literature, we investigate the multifaceted effects of estradiol on key neurotransmitter signaling systems, namely serotonin, dopamine, and glutamate. Findings from rodent models illuminate the impact of hormone manipulations, such as gonadectomy, on the regulation of neuronal brain circuits, providing valuable insights into the connection between hormonal fluctuations and neurotransmitter regulation. Estradiol exerts its effects by binding to three estrogen receptors: estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and G protein-coupled receptor (GPER). Thus, this review explores the promising outcomes observed with estradiol and estrogen receptor agonists administration in both gonadectomized and/or genetically knockout rodents, suggesting potential therapeutic avenues. Despite limited human studies on this topic, the findings underscore the significance of translational research in bridging the gap between preclinical findings and clinical applications. This approach offers valuable insights into the complex relationship between estradiol and neurotransmitter systems. The integration of evidence from neurotransmitter systems and receptor-specific effects not only enhances our understanding of the neurobiological basis of physiological brain functioning but also provides a comprehensive framework for the understanding of possible pathophysiological mechanisms resulting to disease states. By unraveling the complexities of estradiol’s impact on neurotransmitter regulation, this review contributes to advancing the field and lays the groundwork for future research aimed at refining understanding of the relationship between estradiol and neuronal circuits as well as their involvement in brain disorders.

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雌二醇对血清素、谷氨酸和多巴胺系统的影响

雌二醇是雌激素类类固醇激素中最有效和最普遍的成员，在两性中都有表达。作为一种神经活性类固醇，它在调节影响神经元回路和大脑功能（包括学习和记忆、奖励和性行为）的神经递质系统方面发挥着至关重要的作用。这些神经递质系统包括血清素能、多巴胺能和谷氨酸能信号传导途径。因此，本综述探讨了雌二醇及其受体在调节大脑中这些神经递质系统中的关键作用。通过对现有文献的综合分析，我们研究了雌二醇对关键神经递质信号系统（即血清素、多巴胺和谷氨酸）的多方面影响。啮齿动物模型的研究结果阐明了激素操作（例如性腺切除术）对神经元大脑回路调节的影响，为激素波动与神经递质调节之间的联系提供了有价值的见解。雌二醇通过与三种雌激素受体结合发挥作用：雌激素受体α（ERα）、雌激素受体β（ERβ）和G蛋白偶联受体（GPER）。因此，本综述探讨了在性腺切除和/或基因敲除的啮齿动物中使用雌二醇和雌激素受体激动剂观察到的有希望的结果，提出了潜在的治疗途径。尽管关于这一主题的人类研究有限，但研究结果强调了转化研究在弥合临床前研究结果和临床应用之间差距方面的重要性。这种方法为雌二醇和神经递质系统之间的复杂关系提供了有价值的见解。来自神经递质系统和受体特异性效应的证据的整合不仅增强了我们对大脑生理功能的神经生物学基础的理解，而且还为理解导致疾病状态的可能的病理生理机制提供了一个全面的框架。通过揭示雌二醇对神经递质调节影响的复杂性，这篇综述有助于推动该领域的发展，并为未来的研究奠定基础，旨在加深对雌二醇和神经元回路之间的关系及其与大脑疾病的关系的理解。