Abstract :
[en] Steroids are synthesized in the brain and act as neuromodulators to regulate important biological functions such as reproduction, cognition or sensory processing. Songbirds are a tractable model to study the cellular/molecular mechanisms that regulate the production and the sensory coding of learned vocalizations. In zebra finches, estradiol is rapidly synthesized in the auditory cortex (caudomedial nidopallium; NCM) in response to conspecific songs. In both males and females, estradiol is produced in the brain via aromatization of androgens like testosterone, and the aromatase enzyme is densely expressed in NCM. Local estradiol levels within NCM are rapidly elevated when males and females hear song, and local increases in estradiol rapidly enhance the auditory responses of NCM neurons. However, the mechanisms by which estradiol elevations occur within NCM remain unknown. Here, we hypothesize that local estradiol rises during song exposure via an increase in local levels of the androgen substrate, testosterone. The enzyme that regulates testosterone synthesis, 3β-HSD, is present and active in the zebra finch NCM and can be acutely regulated by environmental stimuli. In this study, we assessed testosterone fluctuations within NCM during song exposure using in vivo microdialysis. These fluctuations were assessed in females because of their lower peripheral testosterone levels and higher 3β-HSD activity in NCM as compared to males. In adult females, we observe that local levels of estradiol, but not testosterone, were significantly elevated in the NCM during song playback. By contrast, when the local production of estradiol was concurrently blocked by an aromatase inhibitor, we then observe a massive (>500%) song-evoked increase in testosterone levels within NCM. Furthermore, no significant changes in plasma testosterone were observed in females during song exposure, indicating that the song-evoked peak in NCM testosterone resulted from local brain synthesis and not peripheral fluctuations. Ongoing experiments using an androgen synthesis inhibitor will further test this mechanism of local testosterone production in the brain. Together, these results strongly suggest that elevations in NCM estradiol levels associated with song processing are mediated by a local increase in testosterone production. To our knowledge, this is the first direct evidence showing that testosterone can be synthesized within the brain. As testosterone is currently viewed as a male-typical hormone, these results suggest that its production in the female brain could be critical for fundamental brain functions and behaviors.
