Basic Fibroblast Growth Factor Upregulates Expression of Growth Hormone Gene Through Extracellular Signal-Regulated Kinase 1/2 in Gh4 Cells

Basic fibroblast growth factor (bFGF) is reported to not only play multifunctions in pituitary differentiation and tumor formation, stimulating cell differentiation or proliferation, also stimulate pituitary to secret prolactin, growth hormone (GH) and thyroid stimulating hormone, although obvious effect on growth hormone only responded to high-dose bFGF. Since it is well documented that both bFGF and GH correlate closely to tumorigenesis, development and metastasis, so it is necessary to reveal the relationship between the cytokines. In the present report we investigated the effect of bFGF on transcription level of GH gene in GH4 rat pituitary cells as well as the regulatory mechanism with real-time reverse transcription polymerase chain reaction and western blotting. We observed a significant expressional increase of GH gene in GH4 cells stimulated by bFGF, meanwhile phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) was also found in the cells. Further investigation unveiled that PD98059, a specific inhibitor of ERK1/2 signaling pathway markedly impaired the transcriptional increment of GH gene induced by bFGF in the pituitary cells, which indicates that bFGF upregulates GH gene expression through ERK1/2 signaling pathway in GH4 cells. Results may be helpful to elaborate roles of the two cytokines on tumor (Fig. 3, Ref. 25).