Equol and para-ethyl-phenol stimulate prostaglandin F(2alpha) secretion in bovine corpus luteum: intracellular mechanisms of action.

Corpus luteum (CL) is a reproductive gland that plays a crucial endocrine role in the regulation of the estrous cycle, fertility, and pregnancy in cattle. The main function of CL is secretion of progesterone (P4), an important hormone for establishment a successful pregnancy, whereas prostaglandin F(2alpha) (PGF(2alpha)), 17beta-estradiol (E(2)) and testosterone (T) are implicated in the regulation of luteolysis. It has been shown that phytoestrogens may disrupt numerous reproductive functions on several levels of regulation and via different intracellular mechanisms. Using a cell-culture system of steroidogenic cells of the bovine CL, we determined effects of active phytoestrogen metabolites (equol and para-ethyl-phenol) on PGF(2alpha), P4, and T synthesis in steroidogenic CL cells. Moreover, we examined the intracellular mechanisms of phytoestrogen metabolite actions. Phytoestrogen metabolites did not affect P4 production in steroidogenic CL cells. However, PGF(2alpha) and T were significantly stimulated by metabolites of phytoestrogens in the bovine steroidogenic CL cells. To study the intracellular mechanism of endogenous E(2) and phytoestrogen metabolites action, steroidogenic cells were preincubated with a phospholipase C inhibitor (U73122), a protein kinase C inhibitor (staurosporine), an estrogen receptor antagonist (ICI) and a transcription inhibitor (actinomycin D) for 0.5h, and then stimulated with para-ethyl-phenol, equol or E(2). Only U73122 and staurosporine totally reduced the stimulatory effect of E(2) on PGF(2alpha) production by the cells. ICI and actinomycin D only partially reduced E(2) action on CL cells. In contrast, the stimulatory effect of phytoestrogen metabolites was totally inhibited by ICI and actinomycin D. Moreover, in contrast to E(2) action, phytoestrogen metabolites did not cause intracellular calcium mobilization in the cells. The present study demonstrated that phytoestrogen metabolites stimulate PGF(2alpha) secretion in steroidogenic cells of the bovine CL via the estrogen receptor-dependent, genomic pathway.