Sex hormone receptors and glioblastoma


  • Ashwini K Research Scholar
  • Shilpa S. Shetty
  • Ananthan Raghotham
  • Suchetha Kumari N.
  • Praveen Kumar Shetty



Glioma, Glioblastoma, Sex hormone receptor, Blood Brain Barrier


Glioblastoma (GBM) is the primary brain tumor of the central nervous system which is most common and the most aggressive of all other types of tumors. Current therapy for GBM involves surgical removal (excision) of the tumor followed by radiotherapy with concomitant and adjuvant therapy with temozolomide. Despite the improvement in therapy for GBM, survival of the patients remains poor, only up to 1 year. Treatment for GBM is limited due to the presence of blood brain barrier which prevents the entry of molecules with molecular weight >500 Dalton. Various gene mutations or over expressions lead to GBM growth. Evidence from the earlier reports suggest that epidermal growth factor receptor is overexpressed in 60% of GBM. Interestingly, recent studies have suggested the involvement of sex hormones in the development and progression of GBM though the underlying mechanism of action of these hormones is poorly understood. In this review, we discuss the role of sex hormones and their receptors, a contributing factor in the development of GBM

Author Biographies

Ashwini K, Research Scholar

Department  of  Biochemistry, KS Hegde  Medical  Academy,  Nitte  (Deemed  to  be University),  Mangalore,  Karnataka,  India

Shilpa S. Shetty

Department  of  Biochemistry,  KS Hegde  Medical  Academy,  Nitte  (Deemed  to  be University),  Mangalore,  Karnataka,  India

Ananthan Raghotham

Department  of  Neurosurgery, KS Hegde  Medical  Academy,  Nitte  (Deemed  to  be University),  Mangalore,  Karnataka,  India

Suchetha Kumari N.

Department  of  Biochemistry, KS Hegde  Medical  Academy,  Nitte  (Deemed  to  be University),  Mangalore,  Karnataka,  India

Praveen Kumar Shetty

Department  of  Biochemistry, KS Hegde  Medical  Academy,  Nitte  (Deemed  to  be University),  Mangalore,  Karnataka,  India


World Health Organization. WHO report on cancer: setting priorities, investing wisely and providing care for all. 2020.

Chen, W. P., Xiong, Y., Shi, Y. X., Hu, P. F., Bao, J. P., Wu, L.D. Astaxanthin reduces matrix metalloproteinase expression in human chondrocytes. Int. Immunopharmacol., 2014; 19(1): 174-177.

Choudhury, S., Datta, S., Talukdar, A. D, Choudhury, M. D. Phytochemistry of the Family Bignoniaceae-A review. Assam University Journal of Science and Technology. 2011; 7(1):145-150.

Ostrom, Q. T., Gittleman, H., de Blank, P.M., Finlay, J. L., Gurney, J. G., McKean-Cowdin, R., et al., American brain tumor association adolescent and young adult primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. J. Neurooncol. 2016; 18(suppl_1): i1-50.

O'Brien, E. R., Howarth, C., Sibson, N. R. The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches Front. Cell. Neurosci., 2013; 7:40-53

Shinojima, N., Tada, K., Shiraishi, S., Kamiryo, T., Kochi, M., Nakamura, H., et al., Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res.2003; 63(20): 6962-6970.

Wen, P. Y., Kesari, S. Malignant gliomas in adults. New Eng J Med., 2008; 359(5): 492-507.

Jov?evska, I., Ko?evar, N., Komel, R. Glioma and glioblastoma how much do we (not) know? Molecular and clinical oncology. 2013; 1(6): 935-41.

Liu, G., Yuan, X., Zeng, Z., Tunici, P., Ng, H., Abdulkadir, I. R., et al., Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol. Cancer. 2006; 5(1): 1-2.

Taal, W., Oosterkamp, H. M., Walenkamp, A. M., Dubbink, H. J., Beerepoot, L. V., Hanse, M. C., et al., Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol.2014; 15(9): 943-953.

Özdemir, B. C., Dotto, G. P. Sex hormones and anticancer immunity. Clin. Cancer Res. 2019; 25(15): 4603-4610.

Carlsson, S. K., Brothers, S. P., Wahlestedt, C. Emerging treatment strategies for glioblastoma multiforme EMBO Mol. 2014; 6(11): 1359-1370.

Szopa, W., Burley, T. A., Kramer-Marek, G., Kaspera, W. Diagnostic and therapeutic biomarkers in glioblastoma: current status and future perspectives. Biomed Res. Int., 2017;2017:1-13

Ciocca, D. R., Puy, L. A., Fasoli, L. C. Study of estrogen receptor, progesterone receptor, and the estrogen-regulated Mr 24,000 protein in patients with carcinomas of the endometrium and cervix. Cancer Res. 1989; 49(15): 4298-4304.

Weiser, M. J., Foradori, C. D., Handa, R. J. Estrogen receptor beta in the brain: from form to function. Brain Res. Rev., 2008; 57(2): 309-320.

Sasmita, A.O., Wong, Y.P., Ling, A.P. Biomarkers, and therapeutic advances in glioblastoma multiforme. Asia Pac J Clin Oncol., 2018;14(1):40-51.

Hornung, J., Lewis, C. A., Derntl, B. Sex hormones and human brain function. Handb. Clin. Neurol. 2020; 175: 195-207.

Gruber, C. J., Tschugguel, W., Schneeberger, C., Huber, J. C. Production and actions of estrogens. N. Engl. J. Med. 2002; 346(5): 340-352.

Cunningham, R. L., Lumia, A. R., McGinnis, M. Y. Androgen receptors, sex behavior, and aggression. J. Neuroendocrino., 2012; 96(2): 131-140.

Österlund, M. K., Keller, E., Hurd, Y. L. The human forebrain has discrete estrogen receptor ? messenger RNA expression: high levels in the amygdaloid complex. Neurosci., 1999; 95(2): 333-342.

Wood, R. I., Newman Yu, W. H. A., McGinnis, M. Y. Androgen receptors in cranial nerve motor nuclei of male and female rats. J. Neurobiol.,2001; 46: 1-10.

Davey, R. A., Clarke, M. V., Russell, P. K., Rana, K., Seto, J., Roeszler, K. N., How, J. M. Androgen action via the androgen receptor in neurons within the brain positively regulates muscle mass in male mice. Endocrinol., 2017; 158(10): 3684-3695.

Germán-Castelán, L., Manjarrez-Marmolejo, J., González-Arenas, A., Camacho-Arroyo, I. Intracellular progesterone receptor mediates the increase in glioblastoma growth induced by progesterone in the rat brain. Arch. Med. Res., 2016; 47(6): 419-426.

Gutiérrez-Rodríguez, A., Hansberg-Pastor, V., Camacho-Arroyo, I. Proliferative and invasive effects of progesterone-induced blocking factor in human glioblastoma cells. Biomed Res. Int., 2017;2017:1-10.

Alkharusi, A., Yu, S., Landázuri, N., Zadjali, F., Davodi, B., Nystrom, T. Stimulation of prolactin receptor induces STAT-5 phosphorylation and cellular invasion in glioblastoma multiforme. Oncotarget., 2016; 7(48): 79572-79583.

Piña-Medina, A. G., Hansberg-Pastor, V., González-Arenas, A., Cerbón, M., Camacho-Arroyo, I. Progesterone promotes cell migration, invasion and cofilin activation in human astrocytoma cells. Steroids. 2016; 105: 19-25.

Qu, C., Ma, J., Zhang, Y., Han, C., Huang, L., Shen, L., et al.,Estrogen receptor variant ER??36 promotes tamoxifen agonist activity in glioblastoma cells. Cancer Sci., 2019;110(1): 221-234.

Liu, C., Zhang, Y., Zhang, K., Bian, C., Zhao, Y., Zhang, J. Expression of estrogen receptors, androgen receptor and steroid receptor coactivator-3 is negatively correlated to the differentiation of astrocytic tumors. Cancer Epidemiol., 2014;38(3): 291-297.

Bao, D., Cheng, C., Lan, X., Xing, R., Chen, Z., Zhao, H., et al., Regulation of p53wt glioma cell proliferation by androgen receptor-mediated inhibition of small VCP/p97-interacting protein expression. Oncotarget. 2017; 8(14): 23142.

Lachmann, M., Gelbmann, D., Kalman, E., POLGar, B., Buschle, M., Von Gabain, A., et al., PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome. Int. J. Cancer Res., 2004; 112(1): 51-60.

Sareddy, G.R., Nair, B.C., Gonugunta, V.K., Zhang, Q.G., Brenner, A., Brann, D.W., et al., Therapeutic Significance of Estrogen Receptor ? Agonists in Gliomas Significance of ER? Signaling in Gliomas. Mol. Cancer Ther., 2012;11(5):1174-1182.

Liu, J., Sareddy, G.R., Zhou, M., Viswanadhapalli, S., Li, X., Lai, Z., et al., Differential effects of estrogen receptor ? isoforms on glioblastoma progression. Cancer Res., 2018;78(12): 3176-3189.

Rodríguez-Lozano, D.C., Piña-Medina, A. G., Hansberg-Pastor, V., Bello-Alvarez, C., Camacho-Arroyo, I. Testosterone promotes glioblastoma cell proliferation, migration, and invasion through androgen receptor activation. Front. Endocrinol., 2019; 10: 16-24.

Yu, X., Jiang, Y., Wei, W., Cong, P., Ding, Y., Xiang, L., Wu, K. Androgen receptor signaling regulates growth of glioblastoma multiforme in men. Tumor Biol., 2015; 36(2): 967-972.

Zalcman, N., Canello, T., Ovadia, H., Charbit, H., Zelikovitch, B., Mordechai, A., Fellig, Y., et al., Androgen receptor: a potential therapeutic target for glioblastoma. Oncotarget. 2018; 9(28): 19980 -19993.




How to Cite

Ashwini K, Shilpa S. Shetty, Ananthan Raghotham, Suchetha Kumari N., Praveen Kumar Shetty. Sex hormone receptors and glioblastoma. Biomedicine [Internet]. 2022 Sep. 12 [cited 2022 Sep. 26];42(4):635-40. Available from:

Plum Analytics 

Most read articles by the same author(s)