Centre for Neuroscience, Department of Medicine, Hammersmith Hospital, Imperial College Faculty of Medicine, DuCane Road, London W12ONN, UK.
Pharmacol Rev. 2010 Jun;62(2):155-98. doi: 10.1124/pr.109.002071. Epub 2010 Apr 14.
The classic view of estrogen actions in the brain was confined to regulation of ovulation and reproductive behavior in the female of all mammalian species studied, including humans. Burgeoning evidence now documents profound effects of estrogens on learning, memory, and mood as well as neurodevelopmental and neurodegenerative processes. Most data derive from studies in females, but there is mounting recognition that estrogens play important roles in the male brain, where they can be generated from circulating testosterone by local aromatase enzymes or synthesized de novo by neurons and glia. Estrogen-based therapy therefore holds considerable promise for brain disorders that affect both men and women. However, as investigations are beginning to consider the role of estrogens in the male brain more carefully, it emerges that they have different, even opposite, effects as well as similar effects in male and female brains. This review focuses on these differences, including sex dimorphisms in the ability of estradiol to influence synaptic plasticity, neurotransmission, neurodegeneration, and cognition, which, we argue, are due in a large part to sex differences in the organization of the underlying circuitry. There are notable sex differences in the incidence and manifestations of virtually all central nervous system disorders, including neurodegenerative disease (Parkinson's and Alzheimer's), drug abuse, anxiety, and depression. Understanding the cellular and molecular basis of sex differences in brain physiology and responses to estrogen and estrogen mimics is, therefore, vitally important for understanding the nature and origins of sex-specific pathological conditions and for designing novel hormone-based therapeutic agents that will have optimal effectiveness in men or women.
经典观点认为，雌激素在大脑中的作用仅限于调节所有研究哺乳动物物种（包括人类）的雌性动物的排卵和生殖行为。如今，大量证据表明，雌激素对学习、记忆和情绪以及神经发育和神经退行性过程有深远影响。大多数数据来自女性研究，但越来越多的人认识到，雌激素在男性大脑中也起着重要作用，在男性大脑中，它们可以由循环中的睾酮通过局部芳香化酶产生，也可以由神经元和神经胶质细胞从头合成。因此，基于雌激素的治疗对影响男女两性的大脑疾病具有很大的希望。然而，随着研究开始更仔细地考虑雌激素在男性大脑中的作用，雌激素在男性和女性大脑中具有不同的作用，甚至相反的作用，也具有相似的作用。这篇综述重点介绍了这些差异，包括雌二醇影响突触可塑性、神经递质传递、神经退行性变和认知的能力在雄性大脑中的性别差异，我们认为，这在很大程度上是由于基础电路的组织存在性别差异。几乎所有中枢神经系统疾病（包括神经退行性疾病[帕金森病和阿尔茨海默病]、药物滥用、焦虑和抑郁）的发病率和表现都存在显著的性别差异。因此，了解大脑生理学和对雌激素及雌激素类似物反应中的性别差异的细胞和分子基础，对于理解特定性别病理状况的性质和起源以及设计新的基于激素的治疗剂，使其在男性或女性中具有最佳疗效至关重要。
