雄激素损失通过HPA轴激活加速脑肿瘤生长
雄激素损失通过HPA轴激活加速脑肿瘤生长
作者： 小柯机器人 发布时间：2026/5/7 17:18:10
本期文章：《自然》：Online/在线发表
美国克利夫兰诊所Justin D. Lathia团队取得一项新突破。他们的研究开发出了雄激素损失通过HPA轴激活加速脑肿瘤生长。2026年5月6日，国际知名学术期刊《自然》发表了这一成果。
在这里，小组报道了一个以前未报道的雄激素在脑肿瘤中的抑瘤作用。使用小鼠模型，该课题组人员证明了雄激素的减少通过阉割加速了颅内肿瘤的生长，而在颅外肿瘤中观察到相反的效果（延迟肿瘤生长）。在男性GBM患者中也观察到类似的效果，睾酮治疗显著降低了死亡风险。在患有GBM肿瘤的雄性小鼠中，去势诱导的系统性T由血清糖皮质激素水平升高驱动的细胞功能障碍，其作用于骨髓细胞以促进免疫抑制肿瘤微环境。
在机制上，去势小鼠GBM的下丘脑-垂体-肾上腺轴的过度激活是由IL-1β和TNF增加的神经炎症信号驱动的。空间转录组学分析进一步揭示雄激素缺失增强了小胶质细胞中炎性体的激活，从而促进了这种神经炎症状态。总之，他们的研究结果表明，在雄激素缺乏的情况下，脑肿瘤驱动不同的神经炎症和神经内分泌途径，并突出了抗肿瘤免疫的器官特异性调节。
据介绍，许多癌症，包括胶质母细胞瘤（GBM），显示出男性偏倚的发病率和相关的更差的结果。这种性别差异背后的机制尚不清楚，但可能与部分由性激素（如雄激素）驱动的免疫反应有关。这些激素被认为可以抑制抗肿瘤T细胞免疫和促进肿瘤进展。
附：英文原文
Title: Androgen loss accelerates brain tumour growth via HPA axis activation
Author: Lee, Juyeun, Chung, Yoon-Mi, Silver, Daniel J., Hao, Yue, Harwood, Dylan Scott Lykke, Ealy, Alyssa, Serapiglia, Amanda M., Curtin, Lee, Benedetti, Julia R., Ballard, Christine Ann Pittman, Lapsley, Kamya, Alvarez-Vazquez, Andrea, Goldberg, Jessica, Li, Cathy, Kaur, Sehaj, Neal, Rian, Wang, Sabrina Z., Kay, Kristen E., Volovetz, Josephine, Hong, Ellen S., Fodor, Ray, Jarmula, Jakub, Nicosia, Michael, Rubin, Joshua B., Swanson, Kristin R., Ostrom, Quinn T., Panicker, Nikhil, Kristensen, Bjarne Winther, Berens, Michael, Sharifi, Nima, Lathia, Justin D.
Issue&Volume: 2026-05-06
Abstract: Many cancers, including glioblastoma (GBM), show a male-biased incidence and associated worse outcomes1. The mechanisms that underlie this sex difference remain unclear but may involve an immune response2 that is partly driven by sex hormones such as androgens. Such hormones are thought to suppress antitumour Tcell immunity and to promote tumour progression3,4. However, here we report a previously unreported tumour-suppressive role for androgens in brain tumours. Using mouse models, we demonstrate that androgen loss via castration accelerates intracranial tumour growth, whereas the opposite effect (delayed tumour growth) is observed in extracranial tumours. Similar effects were observed in male patients with GBM, in whom testosterone treatment significantly reduced the risk of death. In male mice with GBM tumours, castration-induced systemic Tcell dysfunction driven by increased levels of serum glucocorticoids, which act on myeloid cells to promote an immunosuppressive tumour microenvironment. Mechanistically, hyperactivation of the hypothalamus–pituitary–adrenal axis in castrated mice with GBM is driven by increased neuroinflammatory signalling through IL-1β and TNF. Spatial transcriptomic analysis further revealed that androgen loss enhances inflammasome activation in microglia, which promotes this neuroinflammatory state. Together, our findings demonstrate that brain tumours drive distinct neuroinflammatory and neuroendocrine pathways in the androgen-deprived setting and highlight organ-specific regulation of antitumour immunity.
DOI: 10.1038/s41586-026-10451-5
Source: https://www.nature.com/articles/s41586-026-10451-5