Phytoestrogens modulate prostaglandin production in bovine endometrium: cell type specificity and intracellular mechanisms.
Prostaglandins (PGs) are known to modulate the proper cyclicity of bovine reproductive organs. The main luteolytic agent in ruminants is PGF2alpha, whereas PGE2 has luteotropic actions. Estradiol 17beta (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 PGF2alpha and PGE2 synthesis 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, PGF2alpha synthesis by both kinds of cells was greater stimulated than PGE2 synthesis. Moreover, epithelial cells treated with phytoestrogens synthesized more PGF2alpha than stromal cells, increasing the PGF2alpha to PGE2 ratio. The epithelial and stromal cells were preincubated with an estrogen-receptor (ER) antagonist (i.e., ICI), a translation 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 PGF2alpha 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 E2 action, phytoestrogens did not cause intracellular calcium mobilization in either epithelial or stromal cells. Phytoestrogens stimulate both PGF2alpha and PGE2 in both cell types of bovine endometrium via an ER-dependent genomic pathway. However, because phytoestrogens preferentially stimulated PGF2alpha synthesis in epithelial cells of bovine endometrium, they may disrupt uterus function by altering the PGF2alpha to PGE2 ratio.
Woclawek-Potocka
Izabela
I
Department of Reproductive Immunology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Acosta
Tomas J
TJ
Korzekwa
Anna
A
Bah
Mamadou M
MM
Shibaya
Masami
M
Okuda
Kiyoshi
K
Skarzynski
Dariusz J
DJ
D000818:Animals; D002417:Cattle; D003609:Dactinomycin / Q000494:pharmacology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D010121:Oxytocin / Q000494:pharmacology; D048789:Phytoestrogens / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011760:Pyrrolidinones / Q000494:pharmacology; D013025:Glycine max; D019311:Staurosporine / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004963:Estrenes; D048789:Phytoestrogens; D011453:Prostaglandins; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D003609:Dactinomycin; D004958:Estradiol; D010121:Oxytocin; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate