Ribeiro M L, Ogando D, Farina M, Franchi A
Laboratorio de Fisio-patología de la preñez y el parto, Centro de Estudios Farmacológicos y Botánicos, Serrano 669, 3rd floor, CP (C1414DEM), Bs As, Argentina.
Prostaglandins Leukot Essent Fatty Acids. 2004 Jan;70(1):33-40. doi: 10.1016/j.plefa.2003.08.003.
The production of prostaglandins (PGs) and nitric oxide (NO) by amnion tissue may play a significant role in parturition. It is thought that epidermal growth factor (EGF) may be one of the fetal signals that governs the initiation of labor. The aim of the present study was to investigate the effect of EGF in vivo on the PGs and nitrite production of rat fetal membranes. We have evaluated the regulation of PGs and nitrite production in rat fetal membranes ex vivo. The intra-uterine administration of EGF 500 ng in day 21 of pregnancy induced increases in PGE(2) (P<0.001) and PGF(2alpha) (P<0.01) compared to the control fetal membranes from pregnant rats on day 22. Also, this dose of EGF diminished nitrate production significantly (P<0.01). We found that fetal membranes at term (days 18-22 of gestation) expressed EGF-R. The NO donor, nitroprussiate 300 and 600 microM, elicited an inhibitory effect on the PGE(2) and PGF(2alpha) stimulated synthesis. On the other hand, indomethacin 10(-6) and 10(-7)M, a non-selective cyclooxygenase inhibitor, reverted the inhibitory effect exerted by EGF. Hence, rat fetal membranes were found to express epidermal growth factor receptors and, under the effect of EGF, PGs and nitrites production pathways interact probably to prevent a toxic effect caused by an exacerbated synthesis of these mediators.
羊膜组织产生前列腺素(PGs)和一氧化氮(NO)可能在分娩过程中发挥重要作用。据认为,表皮生长因子(EGF)可能是控制分娩启动的胎儿信号之一。本研究的目的是研究体内EGF对大鼠胎膜PGs和亚硝酸盐产生的影响。我们已经评估了离体大鼠胎膜中PGs和亚硝酸盐产生的调节情况。与妊娠第22天的妊娠大鼠对照胎膜相比,在妊娠第21天子宫内给予500 ng EGF可导致PGE(2)(P<0.001)和PGF(2α)(P<0.01)增加。此外,该剂量的EGF显著降低了硝酸盐的产生(P<0.01)。我们发现足月胎膜(妊娠第18 - 22天)表达EGF-R。NO供体硝普钠300和600 microM对PGE(2)和PGF(2α)刺激的合成产生抑制作用。另一方面,非选择性环氧化酶抑制剂吲哚美辛10(-6)和10(-7)M可逆转EGF施加的抑制作用。因此,发现大鼠胎膜表达表皮生长因子受体,并且在EGF的作用下,PGs和亚硝酸盐产生途径可能相互作用,以防止这些介质过度合成引起的毒性作用。