Wellbeing of Women

Astle

Astle S, Newton R, Thornton S, Vatish M, Slater DM

Expression and regulation of prostaglandin E synthase isoforms in human myometrium with labour
Astle S, Newton R, Thornton S, Vatish M, Slater DM.
Mol Hum Reprod. 2007 Jan;13(1):69-75.

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 preterm labour.

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). This research has determined:

The immuno-localization of all three PGES enzymes in lower segment pregnant human myometrium;
the expression of PGES and COX-2 mRNA expression at term and preterm gestation with and without labour and;
the effect of interleukin (IL)-1b on COX-2 and PGES mRNA and protein expression in human myometrial smooth muscle (HMSM) cell cultures.

They have shown that 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-1b 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-1b treatment in HMSM cells.

In conclusion, these findings demonstrate the presence of three distinct PGES enzymes in pregnant human myometrium and therefore support a role for locally produced PGE2, possibly produced via COX-2 and mPGES-1 and mPGES-2, in the regulation of myometrial activity. Furthermore, the spatial and labour-associated changes of these enzymes imply distinct physiological functions within the different cell types of the pregnant uterus. Therefore, the further elucidation of the role and regulation of the PGES enzymes, the involvement of the cytokine network and the subsequent signalling via the various EPs is still necessary to understand the mechanisms of parturition.