Hormonal Modulation in Glioma Biology

Hormonal modulation in glioma biology encompasses the multifaceted roles of sex steroids and their receptors in tumour initiation, progression and treatment response. Oestrogens, androgens and progesterone influence glioma cell proliferation, invasion and apoptotic pathways through nuclear and membrane receptors, whose expression often varies across tumour regions and patient sex. Intratumoral synthesis of androgens via upregulated steroidogenic enzymes contributes to an autocrine loop that sustains tumour growth and chemoresistance, while deacetylation of transcription factors by metabolic sensors can amplify receptor-mediated signalling. Selective receptor modulators and agonists targeting oestrogen receptor β have emerged as promising adjuvants to DNA-damaging chemotherapy, enhancing apoptosis and impairing DNA repair. Conversely, androgen receptor antagonists and regulators of Sirt1–FoxO1 axes offer potential to disrupt androgen-driven proliferation. Interplay with key pathways such as Hippo–YAP and DNA damage checkpoints underscores the global significance of hormonal networks in glioma heterogeneity and points to novel strategies for precision therapy.

Research from Nature Portfolio

Selective activation of oestrogen receptor β using a synthetic agonist has been shown to suppress glioblastoma cell growth while sparing normal astrocytes. Treatment reduced cell viability, enhanced apoptosis and sensitised tumours to standard chemotherapeutics by downregulating cell-cycle and DNA repair pathways. In orthotopic and syngeneic models, this approach markedly decreased tumour burden and prolonged survival, demonstrating the therapeutic potential of receptor-specific modulation. Complementary work has revealed that receptor expression alters the DNA damage response: overexpression of oestrogen receptor β attenuates homologous recombination and mismatch repair gene networks, leading to increased DNA breaks and heightened sensitivity to alkylating agents. These findings highlight receptor-driven reprogramming of repair pathways as a strategy to improve chemotherapy efficacy in glioma.

Hormonal Modulation in Glioma Biology publication trend

The graph below shows the total number of articles in hormonal modulation in glioma biology across all publications each year (not limited to Nature Index journals).

Technical terms

Oestrogen receptor β (ERβ): Nuclear receptor that binds oestrogens and modulates transcription of genes governing cell proliferation, apoptosis and DNA repair.

Androgen receptor (AR): Ligand-activated transcription factor that mediates the effects of androgens on cell growth, differentiation and survival.

Selective oestrogen receptor modulator (SERM): Compound exhibiting tissue-specific agonist or antagonist activity at oestrogen receptors, enabling targeted therapeutic effects.

Autocrine synthesis: Process by which cells produce signalling molecules that act upon receptors on the same cell to sustain growth and metabolic programmes.

Sirt1–FoxO1 deacetylation: Post-translational modification where the Sirt1 enzyme removes acetyl groups from the FoxO1 transcription factor, altering its activity and downstream gene expression.

References

1. Estrogen α and β Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model. International Journal of Molecular Sciences (2024).
2. Suppression of FOXO1 activity by SIRT1-mediated deacetylation weakening the intratumoral androgen autocrine function in glioblastoma. Cancer Gene Therapy (2025).
3. The role of PKN1 in glioma pathogenesis and the antiglioma effect of raloxifene targeting PKN1. Journal of Cellular and Molecular Medicine (2023).
4. Selective Estrogen Receptor β Agonist LY500307 as a Novel Therapeutic Agent for Glioblastoma. Scientific Reports (2016).
5. Estrogen receptor beta enhances chemotherapy response of GBM cells by down regulating DNA damage response pathways. Scientific Reports (2019).