Novel insights into GnRH receptor activity : role in the control of human glioblastoma cell proliferation

Abstract. Malignant glioblastoma is one of the highest
proliferative and invasive tumors within the central nervous
system (CNS); the therapeutical options for this disease are
still very poor. Receptors for gonadotropin-releasing
hormone (GnRH) have been reported to be present in glioblastoma
tissues. This study aimed to determine the role of
these receptors in the control of glioma growth. In two
human glioblastoma cell lines, U87MG and U373, we
demonstrated the expression of GnRH receptors, both at
mRNA and protein levels. We also found that GnRH
receptor is expressed in glioblastoma tissues from tumor
patients as shown by Western blotting. In U87MG and U373
cell lines, we found the expression of mRNA for GnRH,
indicating the presence of an autocrine GnRH-based system
in these cell lines. Treatment of the two cell lines with a
GnRH agonist resulted in a significant decrease of cell
proliferation. Moreover, the GnRH agonist significantly
counteracted the forskolin-induced increase of intracellular
cAMP levels in these cells. These findings suggest that the
GnRH receptor might represent a molecular target for an
endocrine therapeutical approach against gliomas.