Motta A B, Estevez A, Franchi A, Perez-Martinez S, Farina M, Ribeiro M L, Lasserre A, Gimeno M F
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo de Investigaciones Científicas y Técnicas (CONICET), Serrano 669, (1414) Buenos Aires, Argentina.
Reproduction. 2001 Apr;121(4):631-7. doi: 10.1530/rep.0.1210631.
Corpus luteum regression is related to an increased generation of reactive oxygen species. Although several studies indicate that PGF(2alpha) is involved in regression of the corpus luteum in mammalian species through an increase in reactive oxygen species, the exact mechanism remains unknown. In the present study, the relationship between nitric oxide and PGF(2alpha) in regulation of lipid peroxidation was studied. Ovarian tissue from pseudopregnant rats at mid- (day 5) or late phase or at the time of regression (day 9 of pseudopregnancy) of corpus luteum development was used. Thiobarbituric acid reactants, used as a lipid peroxidation index, were higher on day 9 of pseudopregnancy than on day 5. In contrast, glutathione content (an antioxidant metabolite) was lower on day 9 than on day 5 of pseudopregnancy. These results indicate that there was an enhanced oxidative status in ovarian tissue during luteolysis. Administration of N(omega)-nitro-L-arginine methyl ester (L-NAME: 600 micromol l(-1)), a competitive nitric oxide synthase (NOS) inhibitor, led to a decrease in basal thiobarbituric acid reactant content in ovarian tissue from rats on day 9 of pseudopregnancy only, indicating that during regression of the corpus luteum, NO could act as intermediary in ovarian lipid peroxidation. Administration of a luteolytic dose (3 microg kg(-1) body weight i.p.) of a synthetic PGF(2alpha) increased thiobarbituric acid reactant content in ovaries from rats on day 9 of pseudopregnancy. As this effect was reversed partially by L-NAME, it is proposed that during regression of corpora lutea, PGF(2alpha) and NO are involved in regulation of lipid peroxidation. As this effect was only reversed partially, it is possible that there is another mechanism involving PGF(2alpha) (but not the NO-NOS pathway) in regulation of ovarian lipid peroxidation. Furthermore, the administration of PGF(2alpha) enhanced ovarian NOS activity, whereas cyclooxygenase inhibition (by indomethacin treatment in vivo) reduced it. As western blotting of ovarian homogenates obtained from PGF(2alpha)-injected rats increased inducible NOS (iNOS) content, it is concluded that PGF(2alpha) enhances both activity and synthesis of NO in rat ovarian tissues during luteolysis. Taken together, these results indicate that in ovaries with regressing corpora lutea, both NO and PGF(2alpha) are involved in part in regulation of lipid peroxidation.
黄体退化与活性氧生成增加有关。尽管多项研究表明，前列腺素F2α（PGF2α）通过增加活性氧参与哺乳动物黄体的退化，但其确切机制仍不清楚。在本研究中，研究了一氧化氮（NO）与PGF2α在调节脂质过氧化中的关系。使用了假孕大鼠在黄体发育中期（第5天）、后期或退化时（假孕第9天）的卵巢组织。作为脂质过氧化指标的硫代巴比妥酸反应物在假孕第9天高于第5天。相反，谷胱甘肽含量（一种抗氧化代谢物）在假孕第9天低于第5天。这些结果表明，在黄体溶解过程中卵巢组织的氧化状态增强。给予N（ω）-硝基-L-精氨酸甲酯（L-NAME：600 μmol l-1），一种竞争性一氧化氮合酶（NOS）抑制剂，仅导致假孕第9天大鼠卵巢组织中基础硫代巴比妥酸反应物含量降低，表明在黄体退化过程中，NO可作为卵巢脂质过氧化的中介。给予溶黄体剂量（3 μg kg-1体重腹腔注射）的合成PGF2α可增加假孕第9天大鼠卵巢中硫代巴比妥酸反应物含量。由于L-NAME可部分逆转这种作用，因此推测在黄体退化过程中，PGF2α和NO参与脂质过氧化的调节。由于这种作用仅被部分逆转，可能存在另一种涉及PGF2α（但不涉及NO-NOS途径）的调节卵巢脂质过氧化的机制。此外，PGF2α的给药增强了卵巢NOS活性，而环氧化酶抑制（通过体内吲哚美辛治疗）则降低了该活性。由于对注射PGF2α的大鼠卵巢匀浆进行蛋白质免疫印迹分析显示诱导型NOS（iNOS）含量增加，因此得出结论，在黄体溶解过程中，PGF2α增强了大鼠卵巢组织中NO的活性和合成。综上所述，这些结果表明，在黄体退化的卵巢中，NO和PGF2α均部分参与脂质过氧化的调节。
