(291) The Effect of Administration and Discontinuation of Finasteride in Male Rats

D. Lee, Y. Choi
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Abstract

It has been suggested that 5AR (5-alpha reductase) inhibitors may have negative effects on psychosexual activity, but there is still debate. We aimed to observe the effect of 5AR type 2 inhibition on brain tissue by using finasteride. 14 weeks old, eight male rats were assigned to each group (group 1 as the control group, group 2 as the finasteride group, and group 3 as the finasteride withdrawal group). Each rat was isolated and acclimatized in a single cage, then mated for 2 days. Rats in group 2 and 3 were administrated with finasteride for 4 weeks, then rats in group 2 were sacrificed whereas rats in group 3 were sacrificed 4 weeks thereafter. Before sacrifice, they were exposed to female bedding at least for 2 days. RT-PCR, western blot, and immunohistochemistry were performed for brain tissue evaluation where the target genes/proteins were 5AR (type 2) and c-Fos. Dihydrotestosterone (ng/dl) and dihydrotestosterone to testosterone ratio (%) plunged after 1 month administration of finasteride (group 2), and they were ameliorated after discontinuation of the drug (group 3) (Figure 1). These results were parallel to those from the western blot and immunohistochemistry (Figure 2 and 3). On the contraty, RT-PCR showed elevation of each gene (5AR and c-Fos) expression (Figure 2). Finasteride exerted an influence on brain tissue including hippocampus and ventromedial preoptic area via 5AR-2 inhibition, resulting in decrease of c-Fos protein activation. However, the negative impact of finasteride on rat brain in regard with c-Fos activation may fall away in a month cessation of the drug. No.
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(291) 雄性大鼠服用和停用非那雄胺的影响
有观点认为,5AR(5-α还原酶)抑制剂可能会对性心理活动产生负面影响,但目前仍存在争议。 我们的目的是使用非那雄胺观察 5AR 2 型抑制剂对脑组织的影响。 我们将 8 只 14 周大的雄性大鼠分为三组(第 1 组为对照组,第 2 组为非那雄胺组,第 3 组为非那雄胺戒断组)。每只大鼠在一个笼子中隔离和适应,然后交配 2 天。给第 2 组和第 3 组大鼠服用非那雄胺 4 周后,第 2 组大鼠被处死,而第 3 组大鼠则在 4 周后处死。处死前,大鼠至少接触雌性被褥 2 天。对脑组织进行 RT-PCR、Western 印迹和免疫组织化学评估,目标基因/蛋白为 5AR(2 型)和 c-Fos。 服用非那雄胺一个月后(第2组),双氢睾酮(ng/dl)和双氢睾酮与睾酮的比率(%)急剧下降,停药后(第3组)情况有所改善(图1)。这些结果与 Western 印迹和免疫组化的结果一致(图 2 和图 3)。另一方面,RT-PCR 显示各基因(5AR 和 c-Fos)的表达均有所升高(图 2)。 非那雄胺通过抑制5AR-2对包括海马和腹外侧视前区在内的脑组织产生影响,导致c-Fos蛋白活化减少。不过,非那雄胺对大鼠大脑c-Fos激活的负面影响可能会在停药一个月后消失。 不
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