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Updated: Jul 16, 2026

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
Published on: January 4, 2018
Egr-1 binds the GnRH promoter to mediate the increase in gene expression by insulin
Sara A DiVall1, Sally Radovick, Andrew Wolfe
1Division of Endocrinology, Department of Pediatrics, Johns Hopkins University, 600 N. Wolfe Street, Park 211, Baltimore, MD 21287, United States. sdivall1@jhmi.edu <sdivall1@jhmi.edu>
Abstract:
Insulin increases gonadotropin-releasing hormone (GnRH) gene expression in in vitro models of GnRH neurons. Early growth response-1 (Egr-1) is a transcription factor that mediates the effect of insulin on target genes. In the GN11 cell line--an immortalized GnRH-secreting neuronal cell line--insulin maximally increases Egr-1 mRNA after 30min of treatment and Egr-1 protein and GnRH mRNA after 60min of treatment. Egr-1 small interfering RNA blocks the insulin-induced increase in GnRH promoter activity, measured as luciferase expression. Chromatin immunoprecipitation using Egr-1 antibody precipitates DNA in a proximal region of the GnRH promoter but not DNA in a distal region. Mutagenesis of a putative Egr-1 binding site within the proximal region blocks the insulin-induced increase in GnRH promoter activity. Thus, Egr-1 binds the GnRH promoter at a site between -67 and -76bp from the transcriptional start site to mediate the insulin-induced increase in GnRH gene transcription.
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