Insights into the role of estrogens and androgens in glial tumorigenesis

Abstract

Gliomas are more common in males than in females. Emerging evidence from several studies in vitro and in vivo have shown the role of estrogens and androgens in glial tumorigenesis. In recent times, studies have also shed light on the actions of estrogen receptors, alpha and beta, and androgen receptor. Here, we provide a comprehensive overview of the research hitherto on estrogens and androgens along with an emphasis on their receptors in glioma pathophysiology. Studies with conflicting results are discussed and future possibilities are put forward. A collective understanding of the studies on these steroid hormones in glioma may serve to create an amalgamated therapeutic approach; and thereby, augment the efforts in tackling this deadly disease.

Androgen deficiency is associated with a better prognosis in glioblastoma

“…In this study, the presence of AD is an independent factor associated with a better prognosis in terms of PFS and OS. This finding is supported by previous works that have shown an increase in the growth and invasiveness of glioblastoma cell lines exposed to testosterone [ 17 , 19 , 20 ]. Furthermore, AR activation by its canonical pathway has been associated with the inhibition of the transforming growth factor-β pathway-induced antiproliferative and proapoptotic response in glioblastoma cells [ 12 ].…”

“…A higher AR expression in glioblastoma biopsies than in the normal brain has been reported [ 12 , 15 – 17 ], and AR expression has been associated with the histological grade of glial tumors; a high AR expression is found whenever the tumoral grade increases [ 18 ]. Regarding the role of the AR in glioblastoma, its activation has been associated with increased proliferation of glioblastoma cells and increases in their migration and invasiveness capacity [ 17 , 19 , 20 ]. Furthermore, in vitro and in vivo studies have shown that silencing the AR gene or its pharmacological blockade led to tumoral cell death [ 15 , 16 , 18 , 21 ].…”

Enzalutamide Induces Apoptotic Insults to Human Drug-Resistant and -Sensitive Glioblastoma Cells via an Intrinsic Bax-Mitochondrion-Cytochrome C Caspase Cascade Activation Pathway

“…In addition, testosterone-AR-transducing signals may contribute to oncogenesis and tumorigenesis of other malignances, including breast, ovary, bladder, lung, liver, and kidney cancers [ 11 ]. Recently, steroid hormones of estrogen and androgen were reported to possibly be involved in the development of glioblastomas [ 12 ]. Thus, the roles of the AR in tumorigenesis of glioblastomas have attracted a lot of research in wide-ranging investigations [ 13 ].…”