Novel insights into GnRH receptor activity: role in the control of human glioblastoma cell proliferation.
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.
Montagnani Marelli
Marina
M
Department of Endocrinology, University of Milano, 20133 Milano, Italy. marina.marellimontagnani@unimi.it
Moretti
Roberta M
RM
Mai
Stefania
S
Müller
Oliver
O
Van Groeninghen
Johan C
JC
Limonta
Patrizia
P
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D017273:Goserelin / Q000494:pharmacology; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011966:Receptors, LHRH / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018931:Antineoplastic Agents, Hormonal; D012333:RNA, Messenger; D011966:Receptors, LHRH; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D000242:Cyclic AMP