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

Abstract

Sex steroids and the neurotrophin brain-derived neurotrophic factor (BDNF) participate in neural tissue formation, phenotypic differentiation, and neuroplasticity. These processes are essential for the health and maintenance of the central nervous system.<h4>Aim</h4>The aim of our review is to elucidate the interaction mechanisms between BDNF and sex steroids in neuronal function.<h4>Method</h4>A series of searches were performed using Mesh terms for androgen/receptors, estrogen/receptors, and BDNF/receptors, and a collection of the scientific data available on PubMed up to February 2025 about mechanical interactions between BDNF and sex steroids was included in this literature review.<h4>Discussion</h4>This review discussed the influence of sex steroids on the formation and/or maintenance of neural circuits via different mechanisms, including the regulation of <i>BDNF</i> expression and signaling. Estrogens exert a time- and region-specific effect on BDNF synthesis. The nuclear estrogen receptor can directly regulate <i>BDNF</i> expression, independently of the presence of estrogen, in neuronal cells, whereas progesterone and testosterone upregulate <i>BDNF</i> expression via their specific nuclear receptors. In addition, testosterone has a positive effect on BDNF release by glial cells, which lack androgen receptors.