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Imperial College Parturition Research Group (V.T., P.R.B.), Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus, London W12 0NN, United Kingdom; Department of Obstetrics and Gynaecology (S.R.S., L.U.K., M.R.J.), Imperial College School of Medicine, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom; and Department of Biological Sciences (S.T.), University of Warwick, Coventry CV4 7AL, United Kingdom
Address all correspondence and requests for reprints to: Dr. Mark R. Johnson, Department of Obstetrics and Gynaecology, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom. E-mail: mark.johnson{at}imperial.ac.uk.
Oxytocin receptor (OTR) expression is increased before the onset of labor in all models of parturition. However, the mechanisms responsible for the increase in OTR expression are uncertain. Animal data suggest that uterine stretch increases OTR mRNA expression. In primary cultures of human uterine smooth muscle cells obtained from nonpregnant (NP) women and pregnant women before (NL) and after (L) the onset of labor, we investigated the effect of stretch on the expression of OTR mRNA and DNA binding of activator protein-1 (AP-1), CCAAT/enhancer binding protein (C/EBP)ß, and nuclear factor-
B transcription factors. OTR expression was least in NL, intermediate in NP, and greatest in L cells. Stretch of NL cells resulted in up-regulation of OTR mRNA expression associated with increased OTR gene promoter activity. Stretch of NP and L cells did not affect OTR mRNA expression. The increased promoter activity was associated with increased DNA binding of C/EBP and AP-1 but not nuclear factor-
B transcription factors. Overexpression of C/EBP, but not AP-1, increased OTR promoter activity. We conclude that stretch of NL cells results in increased OTR mRNA expression probably through increased C/EBPß DNA binding. These data suggest that stretch contributes to the massive increase in OTR expression before the onset of human labor.
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