The Biomolecular Effects of Finasteride on Male Rat Brain during Administration and after Discontinuation

This study aimed to investigate the biomolecular effects of finasteride on rat brain tissue during and after discontinuation.

Twenty-four 14-week-old male Wistar rats were randomly assigned to three groups: Group 1 (control), Group 2 (finasteride-treated), and Group 3 (finasteride-withdrawn). Serum testosterone and dihydrotestosterone levels were measured at the end of the study period. Brain tissues were analyzed using real-time polymerase chain reaction (RT-PCR), western blotting, and immunohistochemistry, with c-Fos employed as a non-specific biomarker of neural cellular activity.

In Group 2, serum dihydrotestosterone levels, 5-alpha reductase type 1 protein expression, and c-Fos phosphorylation showed a decreasing trend (p=0.067, p=0.015, p=0.123, respectively, versus Group 1), but rebounded in Group 3 (p=0.044, p=0.033, p=0.049, respectively, versus Group 2). In contrast, 5-alpha reductase type 2 protein expression was significantly reduced in Group 2 (p=0.017 vs. group 1) and remained suppressed in Group 3 (p=0.029 versus Group 1, p>0.999 versus Group 2). The mean intensity of immunohistochemistry revealed decreased 5-alpha reductase type 2 and c-Fos protein levels in Group 2 (p=0.008 and p=0.017, respectively). After withdrawal, c-Fos protein levels recovered in Group 3 (p=0.031 versus Group 2), whereas 5-alpha reductase type 2 levels remained unchanged (p=0.682 versus Group 2).

Suppression of c-Fos-related neural activity in rat brain tissue could be temporarily maximized by both type 1 and type 2 5-alpha reductase inhibition by finasteride administration, and this suppression could be relieved by the restoration of 5-alpha reductase type 1 expression after finasteride discontinuation.