Decades of work have established the brain as a source of steroid hormones, termed 'neurosteroids'. The neurosteroid neuroestradiol is produced in discrete brain areas and influences cognition, sensory processing, reproduction, neurotransmission, and disease. A prevailing research focus on neuroestradiol has essentially ignored whether its immediate synthesis precursor - the androgen testosterone - is also dynamically regulated within the brain. Testosterone itself can rapidly influence neurophysiology and behavior, and there is indirect evidence that the female brain may synthesize significant quantities of testosterone to regulate cognition, reproduction, and behavior. In songbirds, acoustic communication is regulated by neuroestrogens. Neuroestrogens are rapidly synthetized in the caudomedial nidopallium (NCM) of the auditory cortex of zebra finches in response to song and can influence auditory processing and song discrimination. Here, we examined the in vivo dynamics of NCM levels of the neuroestrogen synthesis precursor, testosterone. Unlike estradiol, testosterone did not appear to fluctuate in the female NCM during song exposure. However, a substantial song-induced elevation of testosterone was revealed in the left hemisphere NCM of females when local aromatization (i.e., conversion to estrogens) was locally blocked. This elevation was eliminated when local androgen synthesis was concomitantly blocked. Further, no parallel elevation was observed in the circulation in response to song playback, consistent with a local, neural origin of testosterone synthesis. To our knowledge, this study provides the first direct demonstration that testosterone fluctuates rapidly in the brain in response to socially-relevant environmental stimuli. Our findings suggest therefore that locally-derived 'neuroandrogens' can dynamically influence brain function and behavior. SIGNIFICANCE STATEMENT: This study demonstrates that androgen synthesis occurs rapidly in vivo in the brain in response to social cues, in a lateralized manner. Specifically, testosterone synthesis occurs within the left secondary auditory cortex when female zebra finches hear male song. Therefore, testosterone could act as a neuromodulator to rapidly shape sensory processing. Androgens have been linked to functions such as the control of female libido, and many steroidal drugs used for contraception, anti-cancer treatments, and sexual dysfunction likely influence the brain synthesis and action of testosterone. The current findings therefore establish a clear role for androgen synthesis in the female brain with implications for understanding neural circuit function and behavior in animals, including humans.

中文翻译：

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雌性鸣鸟大脑中的睾丸激素合成。

数十年来的工作已将大脑确立为类固醇激素（称为“神经类固醇”）的来源。神经甾体神经雌二醇在离散的大脑区域产生，并影响认知，感觉加工，繁殖，神经传递和疾病。一项关于神经雌二醇的流行研究基本上忽略了它的直接合成前体-雄激素睾丸激素-是否也在大脑内动态调节。睾丸激素本身可以迅速影响神经生理和行为，间接证据表明女性大脑可能合成大量的睾丸激素来调节认知，生殖和行为。在鸣禽中，声音交流受神经雌激素调节。响应歌曲，神经雌激素迅速合成在斑马雀科听觉皮层的caudomedian nidopallium（NCM）中，并且可以影响听觉处理和歌曲辨别力。在这里，我们检查了神经雌激素合成前体睾丸激素的NCM水平的体内动力学。与雌二醇不同，在歌唱过程中，女性NCM中的睾丸激素似乎没有波动。然而，当局部芳香化（即转化为雌激素）被局部阻滞时，雌性左半球NCM中会出现歌曲引起的睾丸激素大量升高。当局部雄激素合成被同时阻止时，这种升高被消除。此外，在循环中未观察到响应歌曲播放的平行升高，这与睾丸激素合成的局部，神经起源相一致。就我们所知，这项研究首次直接证明睾丸激素会响应与社会相关的环境刺激而在大脑中快速波动。因此，我们的发现表明，局部衍生的“神经雄激素”可以动态影响大脑的功能和行为。意义声明：这项研究表明，雄激素合成在大脑中会在体内以社交方式快速响应，并以横向方式出现。具体而言，当雌性斑马雀科听到雄性歌曲时，睾丸激素合成发生在左次级听觉皮层内。因此，睾丸激素可以充当神经调节剂，以快速塑造感觉过程。雄激素与功能有关，例如控制女性性欲，许多用于避孕的甾体药物，抗癌治疗，性功能障碍可能会影响大脑的合成和睾丸激素的作用。因此，目前的发现为女性大脑中雄激素的合成确立了明确的作用，对理解动物（包括人）的神经回路功能和行为具有重要意义。