Gong Feng-Ying, Deng Jie-Ying, Shi Yi-Fan
Department of Endocrinology, Beijing Union Medical College Hospital, Chinese Academy of Medical Sciences and Beijing Union Medical College, Beijing, China.
Horm Res. 2003;60(1):14-20. doi: 10.1159/000070822.
To study the effect(s) of interferon gamma (IFN-gamma) on the activity of human growth hormone (hGH) gene promoter in rat pituitary GH3 cells and the molecular mechanism underlying the effect(s).
Cell transfection and luciferase reporter gene were used.
IFN-gamma (10(2) and 10(3) U/ml) increased the activity of hGH in GH3 cells. The addition of the mitogen-activated protein kinase inhibitor PD98059 (40 micromol/l) to the cells blocked the stimulatory effect of IFN-gamma. Neither overexpression of Pit-1 nor inhibiting Pit-1 expression affected IFN-gamma induction of hGH promoter activity. To identify the DNA sequence that mediated the effect of IFN-gamma, four deletion constructs of hGH gene promoter were created. The stimulatory effect of IFN-gamma was abolished following deletion of the -250 to -132 fragment.
IFN-gamma increases the activity of hGH gene promoter in rat pituitary GH3 cells. This stimulatory effect of IFN-gamma appears to require the intracellular mitogen-activated protein kinase-dependent signaling pathway. The effect of IFN-gamma requires the promoter sequence that spans the -250 to -132 fragment of the gene, but is unrelated to Pit-1 protein.
研究γ干扰素（IFN-γ）对大鼠垂体GH3细胞中人生长激素（hGH）基因启动子活性的影响及其作用的分子机制。
采用细胞转染和荧光素酶报告基因技术。
IFN-γ（10²和10³ U/ml）可增加GH3细胞中hGH的活性。向细胞中加入丝裂原活化蛋白激酶抑制剂PD98059（40 μmol/l）可阻断IFN-γ的刺激作用。过表达Pit-1或抑制Pit-1表达均不影响IFN-γ对hGH启动子活性的诱导。为鉴定介导IFN-γ作用的DNA序列，构建了hGH基因启动子的四种缺失构建体。缺失-250至-132片段后，IFN-γ的刺激作用消失。
IFN-γ可增加大鼠垂体GH3细胞中hGH基因启动子的活性。IFN-γ的这种刺激作用似乎需要细胞内丝裂原活化蛋白激酶依赖性信号通路。IFN-γ的作用需要跨越基因-250至-132片段的启动子序列，但与Pit-1蛋白无关。
