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 AP-1, C/EBP and NF-B which may be activated by IL-1 whose concentrations increase with labor.

Objective: To study the effect of IL-1 on OTR expression and the role of AP-1, C/EBP and NF-B in OTR promoter function.

Results: IL-1 induces an increase in OTR mRNA concentrations and OTR ligand binding in myometrial cells, maximal at 4 h and decreased after 20 h. IL-1 activates the transcription factors AP-1 C/EBP and NF-B. Using computer based analysis and EMSA studies we have identified 3 AP-1, 9 C/EBP and 3 NF-B DNA binding sites in the OTR promoter. In transient transfection studies, OTR promoter activity was increased by C/EBP and NF-B by not by AP-1. C/EBP and NF-B together had a synergistic action in induction of OTR promoter activity. Site-directed mutagenesis of each individual C/EBP and NF-B site had no effect upon the ability of either C/EBP or NF-B or the combination of both to activate OTR promoter. However mutation of both of the NF-B sites inhibited promoter activation by NF-B alone but not the combination of C/EBP and NF-B. Deletion studies showed that a region between -851 and -656 of the oxytocin receptor confers responsiveness to the combination of C/EBP and NF-B.

Conclusion: IL-1 has a biphasic effect upon OTR expression in myometrial cells, and C/EBP and NF-B play a synergistic role in OTR promoter activation.