Sex Steroids and Brain-Derived Neurotrophic Factor Interactions in the Nervous System: A Comprehensive Review of Scientific Data

Sex steroids and brain-derived neurotrophic factor (BDNF) participate in neural tissue formation, phenotypic differentiation, and neuroplasticity. All these processes are essential for the health and maintenance of the central nervous system. Aim: To elucidate the interaction mechanisms between BDNF and sex steroids in neuronal function. Method: A series of searches were performed using the Mesh terms for androgen/receptor, estrogens/receptors, and BDNF/receptor, and a collection of the scientific data available on PubMed up to February 2022, on the mechanical interactions between BDNF and sex steroids was included in this literature review. Discussion: Sex steroids influence the formation and/or maintenance of neural circuits via different mechanisms, including the regulation of BDNF expression and signaling. Estrogens exert a time- and region-specific effect on BDNF synthesis. The nuclear estrogen receptor can directly regulate BDNF expression, independently of estrogen presence, in neuronal cells; whereas, progesterone and testosterone upregulate BDNF expression via their specific nuclear receptors. In addition, testosterone has a positive effect on BDNF release by glial cells, which lack androgen receptors.