Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses.
Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses.
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DOI：
10.3389/fnmol.2018.00374
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发表时间：
2018
影响因子：
4.8
通讯作者：
Rosenfeld CS
中科院分区：
文献类型：
--
作者：
Shay DA;Vieira-Potter VJ;Rosenfeld CS
芳香化酶是负责将睾酮转化为雌二醇的酶。在哺乳动物中，芳香化酶在睾丸、卵巢、脑和其他组织中表达。虽然雌激素传统上与女性的生殖和性行为有关，但我们目前的理解将这一观点扩大到包括代谢和认知等生物学功能。现在人们已经认识到芳香化酶在两性的大脑发育和神经行为功能中起着至关重要的终身作用。因此，正在进行的调查试图突出潜在的重要性别差异的芳香化酶的作用，特别是关于其中枢介导的影响。为了表征芳香酶在介导这些功能中的作用，已经确定了芳香酶抑制剂（AI）治疗对人类和动物模型的影响。还采用了全身性缺乏该酶的芳香酶敲除（ArKO）小鼠。编码芳香酶CYP19基因突变的人类也为芳香酶如何以可能的性别依赖方式影响大脑功能提供了重要的见解。更好地了解用于治疗乳腺癌和其他临床疾病的人工智能如何在精神上影响神经行为反应，可能会促进未来治疗方法的发展，以对抗这些影响。在这里，我们将提供一个关键的审查目前的知识芳香化酶调节各种神经行为功能的性别差异。虽然许多物种已被用来更好地了解芳香化酶的功能，这篇评论的重点是啮齿动物模型和人类。我们目前对这一领域的理解的关键差距将被考虑，并将讨论重要的未来研究方向。
Aromatase is the enzyme responsible for converting testosterone to estradiol. In mammals, aromatase is expressed in the testes, ovaries, brain, and other tissues. While estrogen is traditionally associated with reproduction and sexual behavior in females, our current understanding broadens this perspective to include such biological functions as metabolism and cognition. It is now well-recognized that aromatase plays a vital lifetime role in brain development and neurobehavioral function in both sexes. Thus, ongoing investigations seek to highlight potentially vital sex differences in the role of aromatase, particularly regarding its centrally mediated effects. To characterize the role of aromatase in mediating such functions, effects of aromatase inhibitor (AI) treatments on humans and animal models have been determined. Aromatase knockout (ArKO) mice that systemically lack the enzyme have also been employed. Humans possessing mutations in the gene encoding aromatase, CYP19, have also provided critical insight into how aromatase affects brain function in a possible sex-dependent manner. A better understanding of how AIs, used to treat breast cancer and other clinical conditions, may detrimentally affect neurobehavioral responses will likely promote development of future therapies to combat these effects. Herein, we will provide a critical review of the current knowledge of sex differences in aromatase regulation of various neurobehavioral functions. Although many species have been used to better understand the functions of aromatase, this review focuses on rodent models and humans. Critical gaps in our present understanding of this area will be considered, and important future research directions will be discussed.
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