Clarification of the mechanism controlling the regression of corpus luteum by reactive oxygen species

黄体(CL)是一种短暂的内分泌腺，对卵巢周期的调节以及妊娠的建立和维持是必不可少的。黄体退行性变的特征是产生孕酮(P_4)的能力丧失，功能性黄体溶解和组织变性，结构性黄体溶解。前列腺素F_1、前列腺素F_2、前列腺素F_2、前列腺素为了确定PGF和ROS在奶牛CL功能局部调节中的生理作用，本实验研究了1)PGF对牛黄体内皮细胞一氧化氮(NO)生成系统的影响；2)PGF和ROS在牛LECs超氧化物歧化酶(SOD)酶调节中的作用。1)在培养的中期LECs中表达了PGF受体(FPR)mRNA和蛋白。前列腺素F增加NO(亚硝酸盐和…培养的晶状体上皮细胞培养上清液中硝酸盐浓度较高。当1-μ-M-PGF作用于LEC时，PGF不影响内皮型一氧化氮合酶(ENOS)基因和蛋白的表达。另一方面，PGF刺激诱导型一氧化氮合酶(INOS)基因和蛋白的表达。当PGF、H_2O_2或NO供体(NO供体)作用于LECs 2或24 h时，PGF、H_2O_2和NONOate可刺激培养的LECs的一氧化氮合酶活性(P&lt；0.05)，PGF、H_2O_2和NONOate在作用于LEC 2 h时可促进其表达和活性。另一方面，PGF、H_2O_2和NONOate在24 h时可抑制SOD基因和蛋白的表达(P&lt；0.05)。此外，H_2O_2、NONOate和SOD可诱导LECs合成PGF(2 H)。本研究结果表明，牛LECs是PGF的靶点，PGF可能通过刺激LECs的NO生成系统和NOS活性，导致局部NO生成增加，进而导致黄体溶解。总体研究结果表明，牛晶状体上皮细胞中PGF和ROS之间存在正反馈环。在奶牛功能性和结构性黄体溶解过程中，超氧化物歧化酶可能在控制黄体内ROS浓度方面发挥重要作用。较少

Clarification of the mechanism controlling the regression of corpus luteum by reactive oxygen speciesThe corpus luteum (CL) is a transient endocrine gland, which is essential for the regulation of ovarian cycles as well as for establishment and maintenance of pregnancy. The luteal regression is characterized by a loss of the capacity to produce progesterone (P_4) functional luteolysis and tissue degeneration structural luteolysis. Prostaglandin F_<2α> (PGF) and reactive oxygen species (ROS) are implicated in the functional and structural luteolysis. To determine the physiological role of PGF and ROS in the local regulation of CL function in cows, I examined 1) the effect of PGF on nitric oxide (NO) generating system in bovine luteal endothelial cells (LECs) and 2) the roles of PGF and ROS in the regulation of superoxide dismutase (SOD) enzyme in bovine LECs.1) PGF receptor (FPr) mRNA and protein were expressed in cultured LECs obtained from mid-stage CLs. PGF increased NO (nitrite and … More nitrate) concentra- tions in the medium of cultured LECs. When LECs were exposed to 1μM PGF, PGF did not affect the expressions of endothelial NO synthase (eNOS) mRNA and protein. On the other hand, PGF stimulated the expression of inducible NOS (iNOS) mRNA and protein. In addition, PGF stimulated the NOS activity in cultured LECs (P<0.05).2) When LECs were exposed to PGF, H_2O_2 or NONOate (NO donor) for 2 or 24 h. PGF, H_2O_2 and NONOate stimulated SOD mRNA and protein expression, and SOD activity at 2 h (P<0.05). On the other hand, PGF, H_2O_2 and NONOate inhibited SOD mRNA and protein expressions at 24 h (P<0.05). In addition, exposure of LECs to H_2O_2, NONOate and SOD induced an increase in PGF biosynthesis (2 h).The present results indicate that bovine LECs are target for PGF, and suggest that stimulation of the NO generating system and NOS activity induced by PGF result in increasing local NO production followed by luteolysis. The overall findings suggest the presence of a positive feedback loop between PGF and ROS in bovine LECs. SOD may play important roles in controlling the intraluteal ROS concentrations during functional and structural luteolysis in cows. Less