Mechanical stretch up-regulates the human oxytocin receptor in primary human uterine myocytes.
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)beta, and nuclear factor-kappaB 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-kappaB 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/EBPbeta DNA binding. These data suggest that stretch contributes to the massive increase in OTR expression before the onset of human labor.
Terzidou
Vasso
V
Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, London, United Kingdom.
Sooranna
Suren R
SR
Kim
Louise U
LU
Thornton
Steve
S
Bennett
Phillip R
PR
Johnson
Mark R
MR
D000328:Adult; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009215:Myometrium / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D018045:Receptors, Oxytocin / Q000235:genetics*; D013314:Stress, Mechanical; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation
D022782:CCAAT-Enhancer-Binding Protein-beta; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D018808:Transcription Factor AP-1; D004247:DNA; D020928:Mitogen-Activated Protein Kinases