Growth hormone receptor expression and function in meningiomas: effect of a specific receptor antagonist

Object. This study was undertaken to explore the effects of growth hormone (GH) and the GH-stimulated peptide insulin-like growth factor-1 (IGF-1) on the growth rate of meningiomas. Methods. Polymerase chain reaction and ribonuclease protection assays were used to demonstrate that GH receptor messenger RNA was present in all 14 me ningioma specimens studied, regardless of tumor grade. Both wild type (GHRw t) and a previously described exon 3 deletion isoform (GHRd3) of the GH rec eptor were identified in individual tumor specimens. The importance of the GH receptor was assessed using a GH receptor antagonist (B2036). Block ade of the GH receptor with B2036 reduced serum-induced DNA synthesis, as measu red by thymidine incorporation, by 8 to 33% (mean 20%) in primary meningiom a cultures. Tumors that expressed the GHRwt and GHRd3 isoforms, or a combin ation of the two, were all responsive to antagonist treatment. The importan ce of IGF-1 in stimulating meningioma cell growth was also assessed. It was found that IGF-1 increased thymidine incorporation in primary meningioma c ultures in a dose-dependent manner: 1 ng/ml: 5 ng/ml, and 10 ng/ml resulted in increases in thymidine incorporation of 21%, 43%, and 176%, respectivel y, over baseline values. Conclusions. In these studies the authors demonstrate that activation of th e GH/IGF-1 axis significantly increases the growth rate of meningiomas. Blo ckade of the GH receptor on tumor cells inhibited tumor growth. if these fi ndings are confirmed in animal studies, agents that downregulate the GH/IGF -1 axis might represent a potential adjuvant therapy in the management of p atients with meningioma.