Disruption of androgenic signaling has been linked to possible cross-modulation with other hormone-mediated pathways. Therefore, our objective was to explore effects caused by testosterone – T (1, 10 and 50 μM) in peroxisomal signaling of brown trout hepatocytes. To study the underlying paths involved, several co-exposure conditions were tested, with flutamide – F (anti-androgen) and ICI 182,780 – ICI (anti-estrogen). Molecular and morphological approaches were both evaluated. Peroxisome proliferator-activated receptor alpha (PPARα), catalase and urate oxidase were the selected targets for gene expression analysis. The vitellogenin A gene was also included as a biomarker of estrogenicity. Peroxisome relative volumes were estimated by immunofluorescence, and transmission electron microscopy was used for qualitative morphological control. The single exposures of T caused a significant down-regulation of urate oxidase (10 and 50 μM) and a general up-regulation of vitellogenin. A significant reduction of peroxisome relative volumes and smaller peroxisome profiles were observed at 50 μM. Co-administration of T and ICI reversed the morphological modifications and vitellogenin levels. The simultaneous exposure of T and F caused a significant and concentration-dependent diminishing in vitellogenin expression. Together, the findings suggest that in the tested model, T acted via both androgen and estrogen receptors to shape the peroxisomal related targets.

雄激素信号的破坏与其他激素介导的途径可能的交叉调节有关。因此，我们的目标是探讨睾丸激素-T（1、10和50μM）对褐鳟肝细胞过氧化物酶体信号的影响。为了研究涉及的潜在途径，对几种共同暴露条件进行了测试，其中包括氟他米特-F（抗雄激素）和ICI 182,780-ICI（抗雌激素）。分子和形态学方法都进行了评估。过氧化物酶体增殖物激活受体α（PPARα），过氧化氢酶和尿酸氧化酶是基因表达分析的选择靶标。该卵黄蛋白原一该基因也被包括为雌激素的生物标志物。通过免疫荧光估计过氧化物酶体的相对体积，并且将透射电子显微镜用于定性形态控制。T的单次暴露引起尿酸盐氧化酶的显着下调（10和50μM）和卵黄蛋白原的普遍上调。在50μM时观察到过氧化物酶体相对体积的显着减少和更小的过氧化物酶体谱。T和ICI的共同给药逆转了形态学修饰和卵黄蛋白原水平。T和F的同时暴露引起卵黄蛋白原的显着且浓度依赖性的降低表达。总之，这些发现表明，在测试的模型中，T通过雄激素和雌激素受体发挥作用来塑造与过氧化物酶体有关的靶标。