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

阐明活性氧控制黄体退化的机制

基本信息

批准号：
19580326
负责人：
ACOSTA T・j
金额：
$ 2.91万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2007
资助国家：
日本
起止时间：
2007 至 2009
项目状态：
已结题

项目摘要

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

黄体（corpus luteum， 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至关重要。黄体退化的特征是失去产生黄体酮（p4）的能力，功能性黄体溶解和组织退化，结构性黄体溶解。前列腺素F_<2α> (PGF)和活性氧（ROS）参与了功能性和结构性的黄体溶解。为了确定PGF和ROS在奶牛CL功能局部调节中的生理作用，我研究了1)PGF对牛黄体内皮细胞（LECs）一氧化氮（NO）生成系统的影响，2)PGF和ROS对牛黄体内皮细胞超氧化物歧化酶（SOD）酶的调节作用。1) PGF受体（FPr） mRNA和蛋白在培养的中期CLs细胞中表达。PGF增加了培养LECs培养基中的NO（亚硝酸盐和硝酸盐）浓度。当内皮细胞暴露于1μM PGF时，PGF未影响内皮NO合成酶（eNOS） mRNA和蛋白的表达。另一方面，PGF刺激了诱导型NOS (iNOS) mRNA和蛋白的表达。此外，PGF对培养的LECs细胞NOS活性有刺激作用（P<0.05）。2) PGF、H_2O_2和NONOate （NO供体）作用2 h和24 h后，PGF、H_2O_2和NONOate刺激细胞SOD mRNA、蛋白表达和活性（P<0.05）。另一方面，PGF、H_2O_2和NONOate在24 h抑制SOD mRNA和蛋白的表达（P<0.05）。此外，暴露于H_2O_2、NONOate和SOD的LECs诱导PGF生物合成增加（2 h）。上述结果表明，PGF刺激NO生成系统和NOS活性，可增加牛lec的局部NO生成，进而促进黄体溶解。总体结果表明，在牛lec中，PGF和ROS之间存在正反馈回路。SOD可能在奶牛功能性和结构性黄体溶解过程中调控黄体内ROS浓度中起重要作用。少