Activation of epithelial-AR signaling is identified as the major cause of hyperproliferation of the cells during benign and malignant prostate conditions. However, the contribution of stromal-AR is also precarious due to its secretory actions that contribute to the progression of benign and malignant tumors. The present study was aimed to understand the influence of stromal-AR mediated actions on epithelial cells during BPH condition. The secretome (conditioned media-CM) was collected from AR agonist (testosterone-propionate-TP) and antagonist (Nilutamide-Nil) treated BPH patient-derived stromal cells and exposed to BPH epithelial cells. Epithelial cells exhibited increased cell proliferation with the treatment of CM derived from TP-treated stromal cells (TP-CM) but did not support the clonogenic growth of BPH epithelial cells. However, CM derived from Nil-treated stromal cells (Nil-CM) depicted delayed and aggressive BPH epithelial cell proliferation with increased clonogenicity of BPH epithelial cells. Further, decreased AR levels with increased cMyc transcripts and pAkt levels also validated the clonogenic transformation under the paracrine influence of inhibition of stromal-AR. Moreover, the CM of stromal-AR activation imparted positive regulation of basal/progenitor pool through LGR4, β-Catenin, and ΔNP63α expression. Hence, the present study highlighted the restricted disease progression and retains the basal/progenitor state of BPH epithelial cells through the activation of stromal-AR. On the contrary, AR-independent aggressive BPH epithelial cell growth due to paracrine action of loss stromal-AR directs us to reform AR pertaining treatment regimes for better clinical outcomes.

上皮AR信号的激活被确定为良性和恶性前列腺疾病期间细胞过度增殖的主要原因。然而，基质AR的分泌作用也不稳定，这是由于其分泌作用导致良性和恶性肿瘤的进展。本研究旨在了解BPH条件下基质AR介导的作用对上皮细胞的影响。从AR激动剂（睾丸丙酸-TP）和拮抗剂（Nilutamide-Nil）治疗的BPH患者来源的基质细胞中收集分泌组（条件培养基-CM），并将其暴露于BPH上皮细胞。上皮细胞通过处理来自TP处理的基质细胞（TP-CM）的CM表现出增加的细胞增殖，但不支持BPH上皮细胞的克隆生长。然而，源自零处理的基质细胞（Nil-CM）的CM描绘了BPH上皮细胞增殖迟缓和侵袭性增高，BPH上皮细胞的克隆形成能力增强。此外，随着cMyc转录物和pAkt水平的增加，AR水平降低也证实了间质AR抑制的旁分泌作用下的克隆形成转化。此外，间质-AR激活的CM通过LGR4，β-Catenin和ΔNP63α表达赋予了基础/祖细胞正调控。因此，本研究强调了疾病进展受限，并通过基质AR的激活保留了BPH上皮细胞的基础/祖细胞状态。反之，