Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Binding Sites
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Calcium-Calmodulin-Dependent Protein Kinases / drug effects
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Division / drug effects
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Cell Line
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Enzyme Activation / drug effects
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Gonadotropin-Releasing Hormone / drug effects
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Gonadotropin-Releasing Hormone / genetics*
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Gonadotropin-Releasing Hormone / metabolism*
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Humans
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Insulin-Like Growth Factor I / metabolism*
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Insulin-Like Growth Factor I / pharmacology
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Mice
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases*
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Neurons / cytology
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Neurons / metabolism*
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Protein-Tyrosine Kinases / drug effects
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-fos / metabolism
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Receptor, IGF Type 1 / metabolism
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Signal Transduction
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Transcription Factor AP-1 / metabolism
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Transcription, Genetic
Substances
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Proto-Oncogene Proteins c-fos
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RNA, Messenger
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Transcription Factor AP-1
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Gonadotropin-Releasing Hormone
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Insulin-Like Growth Factor I
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Protein-Tyrosine Kinases
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Receptor, IGF Type 1
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases