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

Abstract

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

Materials and methods: 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rats were randomly assigned to three groups: Group 1 (control), Group 2 (finasteride-treated), and Group 3 (finasteride-withdrawn).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.

Results: 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).

Conclusions: 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.