Zhen S, Zakaria M, Wolfe A, Radovick S
Division of Endocrinology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Endocrinol. 1997 Jul;11(8):1145-55. doi: 10.1210/mend.11.8.9956.
A GnRH-expressing neuronal cell line (NLT) was used to determine whether insulin-like growth factor I (IGF-I) regulates GnRH gene expression. A receptor-binding assay demonstrated the expression of IGF-I receptors on NLT cells. Activation of IGF-I receptors induced the Ras/Raf-1/mitogen-activated protein kinase pathway and increased c-fos expression. NLT cells treated with IGF-I underwent cell proliferation and exhibited a growth-independent increase in mouse GnRH mRNA expression. In cells transfected with DNA constructs containing the human GnRH promoter, which includes a consensus AP-1 binding site fused to the luciferase reporter gene, a significant increase in reporter activities was induced by IGF-I, whereas mutation of this AP-1 site significantly reduced IGF-I-induced promoter activation. These results demonstrate that IGF-I serves as an important signal in the regulation of both human and rodent GnRH gene expression.
一种表达促性腺激素释放激素（GnRH）的神经元细胞系（NLT）被用于确定胰岛素样生长因子I（IGF-I）是否调节GnRH基因表达。受体结合试验证明了NLT细胞上IGF-I受体的表达。IGF-I受体的激活诱导了Ras/Raf-1/丝裂原活化蛋白激酶途径并增加了c-fos表达。用IGF-I处理的NLT细胞发生细胞增殖，并在小鼠GnRH mRNA表达上呈现出与生长无关的增加。在转染了包含人GnRH启动子的DNA构建体的细胞中，该启动子包括与荧光素酶报告基因融合的共有AP-1结合位点，IGF-I诱导了报告基因活性的显著增加，而该AP-1位点的突变显著降低了IGF-I诱导的启动子激活。这些结果表明，IGF-I在调节人和啮齿动物GnRH基因表达中均作为重要信号。
