Glioblastomas (GBM) are the most frequent and aggressive primary tumor of the central nervous system. In recent years, it has been proposed that sex hormones such as progesterone play an essential role in GBM biology. Membrane progesterone receptors (mPRs) are a group of G protein–coupled receptors with a wide distribution and multiple functions in the organism. There are five mPRs subtypes described in humans: mPRα, mPRβ, mPRγ, mPRδ, and mPRε. It has been reported that human-derived GBM cells express the mPRα, mPRβ, and mPRγ subtypes, and that progesterone promotes GBM progression in part by mPRα specific activation; however, it is still unknown if mPRδ and mPRε are also expressed in this type of tumor cells. In this study, we characterized the expression and hormonal regulation of mPRδ and mPRε in human GBM cells. We also analyzed a set of biopsies from TCGA. We found that the expression of these receptors is dependent on the tumor’s grade and that mPRδ expression is directly correlated to patients’ survival while the opposite is observed for mPRε. By RT-qPCR, Western blot, and immunofluorescence, the expression of mPRδ and mPRε was detected for the first time in human GBM cells. An in silico analysis showed possible progesterone response elements in the promoter regions of mPRδ and mPRε, and progesterone treatments downregulated the expression of these receptors. Our results suggest that mPRδ and mPRε are expressed in human GBM cells and that they are relevant to GBM biology.

中文翻译：

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mPRδ 和 mPRε 在人胶质母细胞瘤细胞中的作用：表达、激素调节和可能的临床结果。

胶质母细胞瘤（GBM）是中枢神经系统最常见且最具侵袭性的原发性肿瘤。近年来，有人提出黄体酮等性激素在 GBM 生物学中发挥着重要作用。膜孕酮受体（mPR）是一组在生物体内分布广泛、具有多种功能的G蛋白偶联受体。人类有五种 mPR 亚型：mPRα、mPRβ、mPRγ、mPRδ 和 mPRε。据报道，人源性 GBM 细胞表达 mPRα、mPRβ 和 mPRγ 亚型，孕酮部分通过 mPRα 特异性激活促进 GBM 进展；然而，目前尚不清楚mPRδ和mPRε是否也在此类肿瘤细胞中表达。在这项研究中，我们表征了人类 GBM 细胞中 mPRδ 和 mPRε 的表达和激素调节。我们还分析了 TCGA 的一组活检组织。我们发现这些受体的表达取决于肿瘤的分级，并且 mPRδ 表达与患者的生存直接相关，而 mPRε 则相反。通过RT-qPCR、Western blot和免疫荧光，首次在人GBM细胞中检测到mPRδ和mPRε的表达。计算机分析显示 mPRδ 和 mPRε 启动子区域可能存在孕酮反应元件，孕酮治疗下调了这些受体的表达。我们的结果表明 mPRδ 和 mPRε 在人类 GBM 细胞中表达，并且它们与 GBM 生物学相关。