Molecular Human Reproduction, Vol. 10, No. 2, pp. 109-113, 2004
© European Society of Human Reproduction and Embryology 2004
Mechanical stretch activates type 2 cyclooxygenase via activator protein-1 transcription factor in human myometrial cells
1Imperial College Parturition Research Group, Department of Maternal Fetal Medicine, Imperial College School of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH and 2Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus, DuCane Road, London W12 0NN, UK
3 To whom correspondence should be addressed. e-mail: mark.johnson{at}imperial.ac.uk
The uterus is subject to stretch throughout pregnancy, which, in the presence of progesterone, is a potent stimulus for uterine growth. However, in the absence of progesterone or when stretch is excessive, as in multiple pregnancy, it may provoke the onset of labour. We have investigated the effect of stretch on prostaglandin synthesis in primary human uterine myocytes [non-pregnant (NP), pregnant not in labour (NL) and pregnant in labour (L)]. The cells were grown on flexible bottom culture plates and subjected to 1 or 6 h static stretch. Expression of type 2 cyclooxygenase (COX-2) mRNA was similar in samples obtained from NP and L groups and both were significantly greater than those found in the NL group. Stretch of cells from all groups resulted in increased COX-2 mRNA expression. In further studies carried out on cells taken from the NL group, 6 h of stretch resulted in increased COX-2 protein levels and, in the media, increases in prostaglandin (PG) I2 metabolite and PGE2 concentrations and a reduction in the concentration of PGF2
metabolites. After stretch, EMSA studies showed increased activator protein-1 (AP-1) nuclear protein DNA binding activity but not of nuclear factor 
B. These data demonstrate that stretch of human myocytes results in increased COX-2 activity and suggest that this may occur through activation of the AP-1 system.
Key words: Key words: cyclooxygenase-2/labour/myometrium/pregnancy/stretch
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