Role of the prostaglandins in labour and prostaglandin receptor inhibitors in the prevention of preterm labour.
Parturition is composed of five separate but integrated physiological events: fetal membrane rupture, cervical dilatation, myometrial contractility, placental separation, and uterine involution. Prostaglandins (PGs) have central roles in each of these events, but the most studied is myometrial contraction. Elevated uterine PGs or the enhanced sensitivity of the myometrium to PGs leads to contractions and labour. The primary regulator of PG synthesis is the mRNA expression of PG H Synthase (PGHS-2 or COX-2). Given the central role of PGs in labour, this enzyme becomes an obvious therapeutic target for the prevention of preterm labour, the major cause of perinatal mortality and morbidity. Unfortunately, even though the non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit PGHS, are usually successful in suppressing preterm labour or prolonging pregnancy in animal and human studies, the NSAIDS have had adverse effects on fetal physiology and development. Therefore, other means to suppress PG synthesis or action to arrest preterm labour need to be investigated. The PGF2alpha receptor, FP, may prove to be a reasonable target for tocolysis. FP mRNA increases in the mouse uterus at preterm birth, whereas PGF2alpha concentrations do not increase, suggesting elevated uterine sensitivity to contractile agonists is one mechanism for preterm labour initiation. New data shows that administration of a specific FP antagonist, Theratechnologies (THG) 113.31, delays preterm birth in mice and sheep with no observable maternal or fetal side effects. Hence antagonizing PG action offers new hope for delaying preterm birth.
Olson
David M
DM
Perinatal Research Centre, Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada. david.olson@ualberta.ca
Ammann
Christina
C
D000818:Animals; D005260:Female; D006801:Humans; D007743:Labor, Obstetric / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000502:physiology; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015149:Tocolytic Agents / Q000627:therapeutic use*; D014599:Uterus / Q000378:metabolism
D016328:NF-kappa B; D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D015149:Tocolytic Agents; C034671:prostaglandin F2alpha receptor