Secretory and cytosolic phospholipase A2 activities and expression are regulated by oxytocin and estradiol during labor.
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 PLA(2) (cPLA(2)) and types IIA and V of the secretory isoform (sPLA(2)). The aim of this work was to investigate the role of ovarian steroid hormones and oxytocin (OT) in the regulation of rat uterine PLA(2) activity and expression during pregnancy and labor. The activity of sPLA(2) increased near labor, whereas cPLA(2) activity augmented towards the end of gestation. The levels of sPLA(2) IIA and cPLA(2) mRNA showed an increase before labor (P<0.05, day 21), whereas sPLA(2) 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 PLA(2) activities, diminish the expression of sPLA(2) IIA and cPLA(2), as well as decrease PGF(2 alpha) production before the onset of labor (P<0.01). The ovarian steroid did not affect PLA(2) during pregnancy. Collectively, these findings indicate that in the rat uterus, both 17beta-estradiol and OT could be regulating the activity and the expression of the secretory and the cytosolic isoforms of PLA(2), thus controlling PGF(2 alpha) synthesis prior to the onset of labor.
Farina
Mariana Gabriela
MG
Laboratory of Physiopathology of Pregnancy and Labor, School of Medicine, Center for Pharmacological and Botanical Studies, (CEFYBO, CONICET), University of Buenos Aires, Buenos Aires, Argentina. marifarina@yahoo.com
Billi
Silvia
S
Leguizamón
Gustavo
G
Weissmann
Carina
C
Guadagnoli
Tamara
T
Ribeiro
Maria Laura
ML
Franchi
Ana Maria
AM
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D015237:Dinoprost / Q000096:biosynthesis / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000502:physiology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007743:Labor, Obstetric / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology; D010121:Oxytocin / Q000097:blood / Q000502:physiology*; D054467:Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000201:enzymology*; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology
D004965:Estrogen Antagonists; D007527:Isoenzymes; D018045:Receptors, Oxytocin; C047046:atosiban; D013629:Tamoxifen; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D010121:Oxytocin; D015237:Dinoprost; D054467:Phospholipases A2; D014668:Vasotocin