Aim: To study the effect(s) of interferon gamma (IFN-γ) on the activity of human growth hormone (hGH) gene promoter in rat pituitary GH3 cells and the molecular mechanism underlying the effect(s). Methods: Cell transfection and luciferase reporter gene were used. Results: IFN-γ (102 and 103 U/ml) increased the activity of hGH in GH3 cells. The addition of the mitogen-activated protein kinase inhibitor PD98059 (40 µmol/l) to the cells blocked the stimulatory effect of IFN-γ. Neither overexpression of Pit-1 nor inhibiting Pit-1 expression affected IFN-γ induction of hGH promoter activity. To identify the DNA sequence that mediated the effect of IFN-γ, four deletion constructs of hGH gene promoter were created. The stimulatory effect of IFN-γ was abolished following deletion of the –250 to –132 fragment. Conclusions: IFN-γ increases the activity of hGH gene promoter in rat pituitary GH3 cells. This stimulatory effect of IFN-γ appears to require the intracellular mitogen-activated protein kinase-dependent signaling pathway. The effect of IFN-γ requires the promoter sequence that spans the –250 to –132 fragment of the gene, but is unrelated to Pit-1 protein.

Keywords:
Interferon gamma, Human growth hormone gene promoter, Mitogen-activated protein kinase, GH3 cells
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2003
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