These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Regulation of the human oxytocin receptor by nuclear factor-kappaB and CCAAT/enhancer-binding protein-beta.
    Author: Terzidou V, Lee Y, Lindström T, Johnson M, Thornton S, Bennett PR.
    Journal: J Clin Endocrinol Metab; 2006 Jun; 91(6):2317-26. PubMed ID: 16569740.
    Abstract:
    CONTEXT: Increased myometrial sensitivity to oxytocin at term is mediated through increased oxytocin receptor (OTR) expression. OTR promoter contains putative transcription factor-binding sites for activating protein-1 (AP-1), CCAAT/enhancer-binding protein (C/EBP), and nuclear factor-kappaB (NF-kappaB), which may be activated by IL-1beta, whose concentrations increase with labor. OBJECTIVE: The objective of this study was to examine the effect of IL-1beta on OTR expression and the roles of AP-1, C/EBP, and NF-kappaB in OTR promoter function. RESULTS: IL-1beta induces an increase in OTR mRNA concentrations and OTR ligand binding in myometrial cells, which is maximal at 4 h and decreased after 20 h. IL-1beta activates the transcription factors AP-1 C/EBPbeta, and NF-kappaB. Using computer-based analysis and EMSA studies, we have identified three AP-1, nine C/EBP, and three NF-kappaB DNA-binding sites in the OTR promoter. In transient transfection studies, OTR promoter activity was increased by C/EBPbeta and NF-kappaB, but not by AP-1. C/EBPbeta and NF-kappaB together had a synergistic action in the induction of OTR promoter activity. Site-directed mutagenesis of each individual C/EBP and NF-kappaB site had no effect on the ability of C/EBPbeta, NF-kappaB, or their combination to activate OTR promoter. However, mutation of both NF-kappaB sites inhibited promoter activation by NF-kappaB alone, but not that by the combination of C/EBPbeta and NF-kappaB. Deletion studies showed that a region between -851 and -656 of the OTR confers responsiveness to the combination of C/EBPbeta and NF-kappaB. CONCLUSION: IL-1beta has a biphasic effect on OTR expression in myometrial cells, and C/EBP and NF-kappaB play synergistic roles in OTR promoter activation.
    [Abstract] [Full Text] [Related] [New Search]