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Secretory and cytosolic phospholipase A₂ activities and expression are regulated by oxytocin and estradiol during labor

Laboratory of Physiopathology of Pregnancy and Labor, School of Medicine, Center for Pharmacological and Botanical Studies, (CEFYBO, CONICET), National Research Council, University of Buenos Aires, Paraguay 2155, Buenos Aires C1121ABG, Argentina

Correspondence should be addressed to M G Farina; Email: marifarina{at}yahoo.com

The release of arachidonic acid from membrane glycerophospholipids through the action of phospholipases (PLs) is the first step in the biosynthesis of prostaglandins (PGs). In reproductive tissues, the most important PLs are cytosolic PLA₂ (cPLA₂) and types IIA and V of the secretory isoform (sPLA₂). The aim of this work was to investigate the role of ovarian steroid hormones and oxytocin (OT) in the regulation of rat uterine PLA₂ activity and expression during pregnancy and labor. The activity of sPLA₂ increased near labor, whereas cPLA₂ activity augmented towards the end of gestation. The levels of sPLA₂ IIA and cPLA₂ mRNA showed an increase before labor (P<0.05, day 21), whereas sPLA₂ V mRNA was not regulated during pregnancy. The administration of atosiban (synthetic OT antagonist) together with tamoxifen (antagonist of estrogen receptors) was able to decrease cytosolic and secretory PLA₂ activities, diminish the expression of sPLA₂ IIA and cPLA₂, as well as decrease PGF₂ production before the onset of labor (P<0.01). The ovarian steroid did not affect PLA₂ during pregnancy. Collectively, these findings indicate that in the rat uterus, both 17ß-estradiol and OT could be regulating the activity and the expression of the secretory and the cytosolic isoforms of PLA₂, thus controlling PGF₂ synthesis prior to the onset of labor.