Testosterone Modulation of Seizure Susceptibility Is Mediated by Neurosteroids 3α-Androstanediol and 17β-Estradiol

The study investigated the role of testosterone in seizure susceptibility, focusing on its conversion to neurosteroids 3α-androstanediol (3α-Diol) and 17β-estradiol. It was found that testosterone decreased seizure thresholds and increased seizure severity in animal models, effects that were associated with elevated levels of these neurosteroids. The use of letrozole, an aromatase inhibitor, and finasteride, a 5α-reductase inhibitor, demonstrated that blocking the conversion of testosterone to 17β-estradiol and 3α-Diol, respectively, reduced its proconvulsant effects. The study concluded that these testosterone-derived neurosteroids significantly influenced neural excitability and seizure susceptibility.