Phytoestrogens Modulate Prostaglandin Production in Bovine Endometrium: Cell Type Specificity and Intracellular Mechanisms

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.