Farina Mariana Gabriela, Billi Silvia, Leguizamón Gustavo, Weissmann Carina, Guadagnoli Tamara, Ribeiro Maria Laura, Franchi Ana Maria
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.
Reproduction. 2007 Aug;134(2):355-64. doi: 10.1530/REP-07-0078.
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.
通过磷脂酶(PLs)的作用,从膜甘油磷脂中释放花生四烯酸是前列腺素(PGs)生物合成的第一步。在生殖组织中,最重要的磷脂酶是胞质型磷脂酶A2(cPLA2)以及分泌型亚型(sPLA2)的IIA和V型。本研究的目的是探讨卵巢甾体激素和催产素(OT)在妊娠和分娩期间对大鼠子宫磷脂酶A2活性及表达的调节作用。临近分娩时,sPLA2的活性增加,而cPLA2的活性在妊娠末期增强。sPLA2 IIA和cPLA2 mRNA水平在分娩前升高(P<0.05,第21天),而sPLA2 V mRNA在妊娠期间不受调控。将阿托西班(合成的OT拮抗剂)与他莫昔芬(雌激素受体拮抗剂)联合使用,能够降低胞质和分泌型磷脂酶A2的活性,减少sPLA2 IIA和cPLA2的表达,以及在分娩开始前降低前列腺素F2α(PGF2α)的产生(P<0.01)。卵巢甾体激素在妊娠期间不影响磷脂酶A2。总的来说,这些发现表明,在大鼠子宫中,17β-雌二醇和OT都可能调节磷脂酶A2分泌型和胞质型亚型的活性及表达,从而在分娩开始前控制PGF2α的合成。