Skarzynski Dariusz J, Jaroszewski Jerzy J, Okuda Kiyoshi
Department of Reproductive Immunology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima-St. 10, 10-747 Olsztyn, Poland.
Domest Anim Endocrinol. 2005 Aug;29(2):340-6. doi: 10.1016/j.domaniend.2005.02.005. Epub 2005 Feb 24.
Although prostaglandin (PG) F2alpha is known to be a principal luteolytic factor, its action on the bovine corpus luteum (CL) is mediated by other intra-ovarian factors. Tumor necrosis factor-alpha (TNFalpha) and its specific receptors are present in the bovine CL with the highest expressions at luteolysis. TNFalpha in combination with interferon-gamma reduced progesterone (P4) secretion, increased PGF2alpha and leukotriene C4 (LTC4) production, and induced apoptosis of the luteal cells in vitro. Low concentrations of TNFalpha caused luteolysis, which resulted in a decreased level of P4, and increased levels of PGF2alpha, LTC4 and nitrite/nitrate (stable metabolites of nitric oxide-NO) in the blood. Inhibition of local NO production counteracts spontaneous and PGF2alpha-induced luteolysis. Therefore, NO is a likely candidate for the molecule that mediates PGF2alpha and TNFalpha actions during luteolysis. Both PGF2alpha and TNFalpha increase NO concentrations in blood, and stimulate NO synthase expression on protein level in the bovine CL cells. NO stimulates PGF2alpha and LTC4 secretion, inhibits P4 production and reduces the number of viable luteal cells. TNFalpha and NO induce apoptotic death of the CL by modulating expression of bcl-2 family genes and by stimulating expression and activity of caspase-3. The above findings indicate that TNFalpha and NO play crucial roles in functional and structural luteolysis in cattle.
尽管已知前列腺素（PG）F2α是主要的黄体溶解因子，但其对牛黄体（CL）的作用是由其他卵巢内因子介导的。肿瘤坏死因子-α（TNFα）及其特异性受体存在于牛黄体中，在黄体溶解时表达最高。TNFα与干扰素-γ联合使用可降低孕酮（P4）分泌，增加PGF2α和白三烯C4（LTC4）的产生，并在体外诱导黄体细胞凋亡。低浓度的TNFα会导致黄体溶解，从而使血液中P4水平降低，PGF2α、LTC4和亚硝酸盐/硝酸盐（一氧化氮-NO的稳定代谢产物）水平升高。抑制局部NO的产生可抵消自发性和PGF2α诱导的黄体溶解。因此，NO可能是在黄体溶解过程中介导PGF2α和TNFα作用的分子。PGF2α和TNFα均可增加血液中的NO浓度，并在蛋白质水平上刺激牛黄体细胞中NO合酶的表达。NO刺激PGF2α和LTC4的分泌，抑制P4的产生并减少存活黄体细胞的数量。TNFα和NO通过调节bcl-2家族基因的表达以及刺激caspase-3的表达和活性来诱导黄体的凋亡死亡。上述发现表明，TNFα和NO在牛黄体的功能和结构溶解中起关键作用。
