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.
Zhen
S
S
Division of Endocrinology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Zakaria
M
M
Wolfe
A
A
Radovick
S
S
D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D007987:Gonadotropin-Releasing Hormone; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases