Neuroestradiol and neuronal development: Not an exclusive male tale anymore

• Published in: Frontiers in neuroendocrinology Vol. 71; p. 101102
• Main Authors: Garcia-Segura, Luis M., Méndez, Pablo, Arevalo, M. Angeles, Azcoitia, Iñigo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2023
• Subjects: Aromatase; Brain steroidogenesis; Epigenesis, Genetic; Epigenetic regulation; Female; Humans; Kdm6a/Utx; Male; Neuritogenesis; Neurogenesis; Neuronal migration; Neurons - metabolism; Neurosteroids - metabolism; Radial glia; Sex-specific effects; Synaptogenesis; Testosterone - metabolism; Brain steroidogenesis; Neuronal migration; Neuritogenesis; Sex-specific effects; Synaptogenesis; Kdm6a/Utx; Aromatase; Radial glia; Epigenetic regulation; Neurogenesis
• ISSN: 0091-3022; 1095-6808
• DOI: 10.1016/j.yfrne.2023.101102

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•Neuroestradiol is produced by brain steroidogenesis in both sexes.•Neuroestradiol production is boosted in males by testicular testosterone.•Neuroestradiol regulates neurogenesis, neuroblast migration and neuronal differentiation.•Neuroestradiol has sex-specific effects in both sexes.•Epigenetic mechanisms determine sex-specific effects of neuroestradiol.
The brain synthesizes a variety of neurosteroids, including neuroestradiol. Inhibition of neuroestradiol synthesis results in alterations in basic neurodevelopmental processes, such as neurogenesis, neuroblast migration, neuritogenesis and synaptogenesis. Although the neurodevelopmental actions of neuroestradiol are exerted in both sexes, some of them are sex-specific, such as the well characterized effects of neuroestradiol derived from the metabolism of testicular testosterone during critical periods of male brain development. In addition, recent findings have shown sex-specific actions of neuroestradiol on neuroblast migration, neuritic growth and synaptogenesis in females. Among other factors, the epigenetic regulation exerted by X linked genes, such as Kdm6a/Utx, may determine sex-specific actions of neuroestradiol in the female brain. This review evidences the impact of neuroestradiol on brain formation in both sexes and highlights the interaction of neural steriodogenesis, hormones and sex chromosomes in sex-specific brain development.