Phytoestrogens Modulate Prostaglandin Production in Bovine Endometrium: Cell Type Specificity and Intracellular Mechanisms
Phytoestrogens Modulate Prostaglandin Production in Bovine Endometrium: Cell Type Specificity and Intracellular Mechanisms
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DOI：
10.1177/153537020523000506
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发表时间：
2005-05
影响因子：
3.2
通讯作者：
I. Wocławek-Potocka;T. Acosta;A. Korzekwa;M. Bah;M. Shibaya;K. Okuda;D. Skarżyński
中科院分区：
文献类型：
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作者：
I. Wocławek-Potocka;T. Acosta;A. Korzekwa;M. Bah;M. Shibaya;K. Okuda;D. Skarżyński
已知前列腺素（PGs）调节牛生殖器官的正常周期。反刍动物的主要促黄体剂是PGF_（2 α），而PGE_（2 α）具有促黄体作用。E2通过影响PG的合成来调节子宫功能。植物雌激素在结构上类似于E2，具有雌激素活性;因此，它们可能模拟E2对PG合成的影响，并影响生殖系统。使用牛上皮细胞和基质细胞的细胞培养系统，我们确定了植物雌激素的细胞特异性作用（即，大豆苷元，染料木黄酮），它们的代谢物（即，雌马酚和对乙基苯酚）和E2对PGF 2 α和PGE 2合成的影响，并研究了其作用的细胞内机制。植物雌激素及其代谢产物对基质细胞和上皮细胞产生的前列腺素均有显著的刺激作用。然而，两种细胞合成PGF 2 α的刺激大于PGE 2的刺激。此外，用植物雌激素处理的上皮细胞比基质细胞合成更多的PGF 2 α，增加PGF 2 α与PGE 2的比率。将上皮细胞和基质细胞与雌激素受体（ER）拮抗剂（即，ICI）、翻译抑制剂（即，放线菌素D），蛋白激酶A抑制剂（即，星形孢菌素），和磷脂酶C抑制剂（即，U 73122）作用0.5小时，然后用雌马酚、对乙基苯酚或E2刺激。尽管E2对PGF_（2 α）合成的作用被所有试剂阻断，但植物雌激素的刺激作用仅被ICI和放线菌素D阻断。此外，在相反的E2作用，植物雌激素没有引起细胞内钙动员上皮细胞或基质细胞。植物雌激素通过ER依赖性基因组途径刺激牛子宫内膜两种细胞类型中的PGF 2 α和PGE 2。然而，由于植物雌激素优先刺激牛子宫内膜上皮细胞中PGF 2 α的合成，它们可能通过改变PGF 2 α与PGE 2的比例来破坏子宫功能。
Prostaglandins (PGs) are known to modulate the proper cycllcity of bovine reproductive organs. The main luteolytlc agent in ruminants Is PGF2α, whereas PGE2 has luteotropic actions. Estradiol 17ß (E2) regulates uterus function by influencing PG synthesis. Phytoestrogens structurally resemble E2 and possess estrogenic activity; therefore, they may mimic the effects of E2 on PG synthesis and influence the reproductive system. Using a cell-culture system of bovine epithelial and stromal cells, we determined cell-specific effects of phytoestrogens (i.e., daidzein, genistein), their metabolites (i.e., equol and para-ethyl-phenol, respectively), and E2 on PGF2α and PGE2synthesis and examined the intracellular mechanisms of their actions. Both PGs produced by stromal and epithelial cells were significantly stimulated by phytoestrogens and their metabolites. However, PGF2α synthesis by both kinds of cells was greater stimulated than PGE2 synthesis. Moreover, epithelial cells treated with phytoestrogens synthesized more PGF2α than stromal cells, increasing the PGF2α, to PGE2 ratio. The epithelial and stromal cells were prelncubated with an estrogen-receptor (ER) antagonist (i.e., ICI), a transiation inhibitor (i.e., actinomycin D), a protein kinase A inhibitor (i.e., staurosporin), and a phospholipase C inhibitor (i.e., U73122) for 0.5 hrs and then stimulated with equol, para-ethyl-phenol, or E2- Although the action of E2 on PGF2α synthesis was blocked by all reagents, the stimulatory effect of phytoestrogens was blocked only by ICI and actinomycin D in both cell types. Moreover, in contrast to E2action, phytoestrogens did not cause Intracellular calcium mobilization in either epithelial or stromal cells. Phytoestrogens stimulate both PGF2α and PGE2 in both cell types of bovine endometrium via an ER-dependent genomic pathway. However, because phytoestrogens preferentially stimulated PGF2α synthesis in epithelial cells of bovine endometrium, they may disrupt uterus function by altering the PGF2α to PGE2 ratio.