Regulation of Gonadotropin-Releasing Hormone (GnRH) Gene Expression by Insulin-Like Growth Factor I in a Cultured GnRH-Expressing Neuronal Cell Line

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.