Androgen Loss Accelerates Brain Tumour Growth in Mouse Models

Androgen loss accelerates the growth of brain tumours in mouse models while producing the opposite effect in tumours outside the brain, according to a research paper published by Nature. The study found that castration in male mice with glioblastoma led to faster intracranial tumour progression. In contrast, the same androgen deprivation delayed growth of extracranial tumours.

Similar patterns appeared in data from male patients with glioblastoma, where testosterone treatment was linked to a significantly lower risk of death. In the mouse models, castration triggered systemic T cell dysfunction driven by increased serum glucocorticoid levels. These glucocorticoids acted on myeloid cells to create an immunosuppressive tumour microenvironment.

The paper states that hyperactivation of the hypothalamus–pituitary–adrenal axis in castrated mice carrying glioblastoma tumours was driven by increased neuroinflammatory signalling through IL-1β and TNF. Spatial transcriptomic analysis showed that androgen loss enhanced inflammasome activation in microglia, further promoting the neuroinflammatory state.

The findings indicate that brain tumours engage distinct neuroinflammatory and neuroendocrine pathways under androgen deprivation.

The results highlight organ-specific regulation of antitumour immunity. Many cancers, including glioblastoma, exhibit higher incidence and worse outcomes in males. Previous research had suggested that androgens generally suppress antitumour T cell responses and promote tumour progression.

The new paper reports a previously unreported tumour-suppressive role for androgens specifically in brain tumours. >The mechanisms that underlie this sex difference remain unclear but may involve an immune response that is partly driven by sex hormones such as androgens.