Wartalski Kamil, Wiater Jerzy, Maciak Patrycja, Pastuła Agnieszka, Lis Grzegorz J, Samiec Marcin, Trzcińska Monika, Duda Małgorzata
Department of Histology, Jagiellonian University Medical College, Kopernika 7 Street, 31-034 Krakow, Poland.
Department of Endocrinology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University in Krakow, Gronostajowa 9 Street, 30-387 Krakow, Poland.
Int J Mol Sci. 2024 Feb 29;25(5):2833. doi: 10.3390/ijms25052833.
Boldenone (Bdn) and nandrolone (Ndn) are anabolic androgenic steroids (AASs) that, as our previous studies have shown, may increase the risk of neoplastic transformation of porcine ovarian putative stem cells (poPSCs). The NF-κB pathway may be important in the processes of carcinogenesis and tumour progression. Therefore, in this work, we decided to test the hypothesis of whether Bdn and Ndn can activate the NF-κB pathway by acting through the membrane androgen receptor ZIP-9. For this purpose, the expression profiles of both genes involved in the NF-κB pathway and the gene coding for the ZIP-9 receptor were checked. The expression and localization of proteins of this pathway in poPSCs were also examined. Additionally, the expression of the ZIP-9 receptor and the concentration of the NF-κB1 and 2 protein complex were determined. Activation of the NF-κB pathway was primarily confirmed by an increase in the relative abundances of phosphorylated forms of RelA protein and IκBα inhibitor. Reduced quantitative profiles pinpointed not only for genes representing this pathway but also for unphosphorylated proteins, and, simultaneously, decreased concentration of the NF-κB1 and 2 complex may indicate post-activation silencing by negative feedback. However, the remarkably and sustainably diminished expression levels noticed for the gene and ZIP-9 protein suggest that this receptor does not play an important role in the regulation of the NF-κB pathway.
Boldenone(Bdn)和nandrolone(Ndn)是合成代谢雄激素类固醇(AASs),正如我们之前的研究所表明的,它们可能会增加猪卵巢假定干细胞(poPSCs)发生肿瘤转化的风险。NF-κB通路在致癌和肿瘤进展过程中可能很重要。因此,在这项研究中,我们决定检验Bdn和Ndn是否能通过膜雄激素受体ZIP-9激活NF-κB通路这一假设。为此,我们检测了NF-κB通路中相关基因以及ZIP-9受体编码基因的表达谱。我们还研究了该通路蛋白在poPSCs中的表达和定位。此外,我们测定了ZIP-9受体的表达以及NF-κB1和2蛋白复合物的浓度。NF-κB通路的激活主要通过RelA蛋白和IκBα抑制剂磷酸化形式的相对丰度增加得到证实。定量分析结果不仅显示了该通路相关基因的减少,还显示了未磷酸化蛋白的减少,同时,NF-κB1和2复合物浓度的降低可能表明存在负反馈导致的激活后沉默。然而,ZIP-9基因和蛋白显著且持续降低的表达水平表明该受体在NF-κB通路的调节中并不起重要作用。