Preterm labour occurs in approximately 10 % of pregnancies and shows no signs of
abating. Prostaglandin E2 (PGE2) synthesis plays a regulatory role in a number of
important processes that are necessary for successful labour. One role for PGE2 is the
activation of contractility in the muscle that contracts during labour, the myometrium.
The myometrium is theorised to separate into two functional compartments during
pregnancy and parturition. During parturition, the fundal region contracts
downwards, whilst the lower segment relaxes. PGE2 binds to four G-protein coupled
receptors, termed E-series (EP1-4), which modulate a dynamic range of responses due
to differential binding of G proteins. The accepted theory for the function of EP
receptors in the myometrium, at the time of labour, is that EP1 and EP3 are procontractile
receptors whilst EP2 and EP4 receptors are anti-contractile. This thesis
studied the compartmental expression of the EP receptors and the signalling pathways
they couple to in the pregnant myometrium. EP receptor mRNA and protein do not
alter in expression between sample groups, before or after the onset of labour.
Further experiments identified EP2 receptors to activate both pro- and anti-labour
responses (expression of COX-2 and inhibition of myometrial contractility),
interestingly by two distinct G protein signalling pathways, questioning its role as an
anti-labour receptor. A novel EP4 receptor agonist also activated cell signalling
pathways not previously associated with this receptor. An EP3, but not an EP1,
antagonist inhibited spontaneous and PGE2 induced contractility, despite the
activation of similar signalling pathways. Overall, this study indicates that the action
of an individual EP receptor is more diverse than anticipated, indicating that the
myometrium is a complex, dynamic system enabling efficient reprogramming of
responsiveness during pregnancy and labour
