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Mol. Hum. Reprod. Advance Access published online on November 14, 2006
Molecular Human Reproduction, doi:10.1093/molehr/gal093
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received August 13, 2006
Revised October 2, 2006
Accepted October 9, 2006

Article

Expression and regulation of prostaglandin E synthase isoforms in human myometrium with labour

S. Astle 1, R. Newton 2, S. Thornton 1, M. Vatish 1, and D.M. Slater 3 *

1 Clinical Sciences Research Institute, Warwick Medical School, UHCW Trust, Coventry, UK
2 Department of Cell Biology & Anatomy, Faculty of Medicine, University of Calgary, Alberta, Canada
3 Clinical Sciences Research Institute, Warwick Medical School, UHCW Trust, Coventry, UK; Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Alberta, Canada

* To whom correspondence should be addressed.
D.M. Slater, E-mail: d.m.slater{at}warwick.ac.uk


  Abstract

Since the controversies regarding the use of non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase (COX)-2 antagonists for the treatment of preterm labour (PTL), more emphasis has been placed on investigating the terminal synthases involved in the production of prostaglandins (PGs) to allow more targeted therapy in PTL. Prostaglandin E2 (PGE2) is synthesized by one of three enzymes, cytosolic prostaglandin E synthase (cPGES), microsomal PGES-1 (mPGES-1) and microsomal PGES-2 (mPGES-2). We have determined (i) the immuno-localization of all three PGES enzymes in lower segment pregnant human myometrium, (ii) the expression of PGES and COX-2 mRNA expression at term and preterm gestation with and without labour and (iii) the effect of interleukin (IL)-1{beta} on COX-2 and PGES mRNA and protein expression in human myome-trial smooth muscle (HMSM) cell cultures. We show mPGES-1 protein located predominantly in myometrial and vascular smooth muscle cells (SMCs), whilst mPGES-2 protein is largely in stromal cells surrounding the SMC and cPGES is diffusely located throughout the myometrium. Expression of mPGES-2 mRNA increased with term labour and PTL and expression of COX-2 and mPGES-1 mRNA with term labour, whereas cPGES expression did not change. IL-1{beta} by stimulated release of PGE2 by HMSM cells and increased COX-2 and mPGES-1 mRNA and protein expression. Thus, COX-2 expression and mPGES-1 expression are co-ordinately up-regulated in lower segment myometrium with term labour and with IL-1{beta} treatment in HMSM cells.

Keywords: prostaglandin E2 synthase/myometrium/labour/myometrial smooth muscle.
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