Biomedical Center Munich (BMC), Cell Biology, Anatomy III, Faculty of Medicine, Ludwig-Maximilian-University (LMU) Munich, Planegg-Martinsried, Germany.
Laboratory for Functional Genome Analysis LAFUGA, Gene Center, LMU Munich, Munich, Germany.
Mol Hum Reprod. 2023 Aug 30;29(9). doi: 10.1093/molehr/gaad029.
The cation channel 'transient receptor potential vanilloid 2' (TRPV2) is activated by a broad spectrum of stimuli, including mechanical stretch, endogenous and exogenous chemical compounds, hormones, growth factors, reactive oxygen species, and cannabinoids. TRPV2 is known to be involved in inflammatory and immunological processes, which are also of relevance in the ovary. Yet, neither the presence nor possible roles of TRPV2 in the ovary have been investigated. Data mining indicated expression, for example, in granulosa cells (GCs) of the human ovary in situ, which was retained in cultured GCs derived from patients undergoing medical reproductive procedures. We performed immunohistochemistry of human and rhesus monkey ovarian sections and then cellular studies in cultured GCs, employing the preferential TRPV2 agonist cannabidiol (CBD). Immunohistochemistry showed TRPV2 staining in GCs of large antral follicles and corpus luteum but also in theca, endothelial, and stromal cells. TRPV2 transcript and protein levels increased upon administration of hCG or forskolin. Acutely, application of the agonist CBD elicited transient Ca2+ fluxes, which was followed by the production and secretion of several inflammatory factors, especially COX2, IL6, IL8, and PTX3, in a time- and dose-dependent manner. CBD interfered with progesterone synthesis and altered both the proteome and secretome, as revealed by a proteomic study. While studies are somewhat hampered by the lack of highly specific TRPV2 agonist or antagonists, the results pinpoint TRPV2 as a modulator of inflammation with possible roles in human ovarian (patho-)physiology. Finally, as TRPV2 is activated by cannabinoids, their possible ovarian actions should be further evaluated.
阳离子通道“瞬时受体电位香草酸 2”(TRPV2) 可被多种刺激激活，包括机械拉伸、内源性和外源性化学物质、激素、生长因子、活性氧和大麻素。TRPV2 已知参与炎症和免疫过程，这在卵巢中也很重要。然而，尚未研究 TRPV2 在卵巢中的存在及其可能的作用。数据挖掘表明，例如，在人类卵巢原位的颗粒细胞(GCs)中表达，这种表达在接受医学生殖程序的患者衍生的培养 GCs 中得以保留。我们对人类和恒河猴卵巢切片进行了免疫组织化学研究，然后在培养的 GCs 中进行了细胞研究，使用了首选 TRPV2 激动剂大麻二酚(CBD)。免疫组织化学显示，TRPV2 在大腔卵泡和黄体的 GCs 中以及在卵泡膜细胞、内皮细胞和基质细胞中染色。给予 hCG 或 forskolin 后，TRPV2 转录本和蛋白水平增加。激动剂 CBD 的急性应用会引起短暂的 Ca2+ 通量，随后以时间和剂量依赖的方式产生和分泌几种炎症因子，尤其是 COX2、IL6、IL8 和 PTX3。CBD 干扰孕激素合成，并通过蛋白质组学研究改变蛋白质组和分泌组。虽然由于缺乏高度特异性的 TRPV2 激动剂或拮抗剂，研究受到了一定的阻碍，但结果表明 TRPV2 是一种炎症调节剂，在人类卵巢(病理)生理学中可能具有作用。最后，由于 TRPV2 可被大麻素激活，因此应进一步评估其对卵巢的可能作用。
