Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy.
Biomolecules. 2022 Oct 26;12(11):1567. doi: 10.3390/biom12111567.
The treatment with finasteride (i.e., an inhibitor of 5α-reductase) may be associated with different side effects (i.e., depression, anxiety, cognitive impairment and sexual dysfunction) inducing the so-called post finasteride syndrome (PFS). Moreover, previous observations in PFS patients and an experimental model showed alterations in gut microbiota populations, suggesting an inflammatory environment. To confirm this hypothesis, we have explored the effect of chronic treatment with finasteride (i.e., for 20 days) and its withdrawal (i.e., for 1 month) on the levels of steroids, neurotransmitters, pro-inflammatory cytokines and gut permeability markers in the colon of adult male rat. The obtained data demonstrate that the levels of allopregnanolone (ALLO) decreased after finasteride treatment and after its withdrawal. Following the drug suspension, the decrease in ALLO levels correlates with an increase in IL-1β and TNF-α, serotonin and a decrease in dopamine. Importantly, ALLO treatment is able to counteract some of these alterations. The relation between ALLO and GABA-A receptors and/or pregnenolone (ALLO precursor) could be crucial in their mode of action. These observations provide an important background to explore further the protective effect of ALLO in the PFS experimental model and the possibility of its translation into clinical therapy.
非那雄胺（5α-还原酶抑制剂）治疗可能与不同的副作用（如抑郁、焦虑、认知障碍和性功能障碍）相关，导致所谓的非那雄胺治疗后综合征（PFS）。此外，PFS 患者和实验模型中的先前观察结果表明肠道微生物群发生改变，提示存在炎症环境。为了证实这一假设，我们探索了慢性非那雄胺治疗（即 20 天）及其停药（即 1 个月）对成年雄性大鼠结肠中类固醇、神经递质、促炎细胞因子和肠道通透性标志物水平的影响。获得的数据表明，非那雄胺治疗后和停药后，别孕烯醇酮（ALLO）的水平降低。停药后，ALLO 水平的降低与 IL-1β 和 TNF-α、血清素增加以及多巴胺减少相关。重要的是，ALLO 治疗能够抵消其中一些变化。ALLO 与 GABA-A 受体和/或孕烯醇酮（ALLO 前体）之间的关系可能对其作用模式至关重要。这些观察结果为进一步探索 ALLO 在 PFS 实验模型中的保护作用以及将其转化为临床治疗的可能性提供了重要背景。
