Central aromatization: A dramatic and responsive defense against threat and trauma to the vertebrate brain

• Published in: Frontiers in neuroendocrinology 2020-01, Vol.56, p.100816-100816, Article 100816
• Main Authors: Duncan, Kelli A., Saldanha, Colin J.
• Format: Article
• Language: English
• Subjects: Animals; Aromatase - genetics; Aromatase - metabolism; Astrocytes - enzymology; Brain - enzymology; Brain Edema - enzymology; Brain Injuries - enzymology; Estradiol - physiology; Estrogen; Female; Humans; Inflammation; Inflammation - enzymology; Male; Nerve Degeneration - enzymology; Neuroprotection; Neuroprotection - physiology; Songbird; Songbirds - physiology; Traumatic brain injury; Up-Regulation
• ISSN: 0091-3022; 1095-6808
• DOI: 10.1016/j.yfrne.2019.100816

•Estrogens are established effectors of sex-specific neural circuits.•Astrocytic aromatization is upregulated in response to a broad range of brain damage.•Estrogens synthesized by astrocytic aromatization potently inhibit neuroinflammation.•Neural aromatization may also protect the brain against peripheral inflammation and infection. Aromatase is the requisite and limiting enzyme in the production of estrogens from androgens. Estrogens synthesized centrally have more recently emerged as potent neuroprotectants in the vertebrate brain. Studies in rodents and songbirds have identified key mechanisms that underlie both; the injury-dependent induction of central aromatization, and the protective effects of centrally synthesized estrogens. Injury-induced aromatase expression in astrocytes occurs following a broad range of traumatic brain damage including excitotoxic, penetrating, and concussive injury. Responses to neural insult such as edema and inflammation involve signaling pathways the components of which are excellent candidates as inducers of this astrocytic response. Finally, estradiol from astrocytes exerts a paracrine neuroprotective influence via the potent inhibition of inflammatory pathways. Taken together, these data suggest a novel role for neural aromatization as a protective mechanism against the threat of inflammation and suggests that central estrogen provision is a wide-ranging neuroprotectant in the vertebrate brain.