Aromatase as a Central Node in Astrocyte Health and Homeostasis

Aromatase is well recognized for its role in estrogen synthesis; however, most research to date has focused on neuronal aromatase, leaving its astrocyte-specific functions, such as homeostasis, inflammation, stress adaptation, and metabolic regulation, comparatively underexplored. Given the crucial roles of astrocytes and brain-derived estrogens in maintaining neural health and modulating disease processes, a deeper understanding of how aromatase shape astrocytic function has become increasingly necessary. Yet, attributing these effects solely to astrocytic aromatase is complicated by the paracrine and endocrine actions of estradiol. This scoping review synthesizes current evidence on how aromatase activity modulates astrocytic functions, identifies key knowledge gaps, and outlines priorities for future research. Using the Population, Concept, Context (PCC) framework, primary research studies across multiple species and experimental contexts were examined. The evidence consistently shows that astrocytic aromatase is upregulated following injury or stress, reflecting a conserved neuroprotective response mediated by local estrogen synthesis. Aromatase activity modulates neuroinflammation by suppressing pro-inflammatory cytokine production and limiting gliosis, while also enhancing astrocytic metabolic resilience, particularly under oxidative or nitrosative stress, thereby supporting neuronal fate in both in vitro and in vivo models. Across studies, sex differences have emerged, with female models often exhibiting higher aromatase expression and more pronounced neuroprotective effects. Despite compelling pre-clinical evidence, human-centered studies remain limited, thereby constraining the translational potential of current knowledge. Moreover, the molecular interplay between aromatase-driven estrogen signaling and other neurosteroidogenic pathways is not yet fully elucidated. Overall, while astrocytic aromatase appears to act as a pivotal regulator of CNS homeostasis and repair, particularly in the context of injury and neurodegeneration, current evidence does not fully disentangle its role from estradiol derived from neurons or systemic sources. These insights highlight its therapeutic potential for modulating inflammation and enhancing brain resilience and underscore the need for sex-specific, human-based research.