Mifepristone and PGF₂α activate phosphatidylinositol hydrolysis in the ovine corpus luteum

Two experiments were conducted to determine whether mifepristone (RU486) and PGF₂α activate the phosphatidylinositol hydrolysis pathway during the midluteal phase of the ovine estrous cycle. In experiment 1, ewes on day 8 of the cycle were given 10 μg RU486 or vehicle into the ovarian artery with removal of the corpus luteum (CL) after 10 min. Blood collected prior to and after treatment was analyzed for progesterone. Aliquots of CL were incubated with 10 μCi of ³H-inositol and in the presence and absence of PGF₂α (10 nM) for 15 min. Exposure of CL to RU486 and PGF₂α increased phosphatidylinositol hydrolysis (p < 0.05). Serum progesterone was reduced in both control and RU486-treated ewes (p < 0.05) compared to concentrations before treatments. In experiment 2, aliquots of CL collected from ewes on day 8 of the cycle were incubated with ³H-inositol and exposed to RU486 (2 μM) in the presence and absence of PGF₂α (1 μM) for 15 min. Treatments stimulated phosphatidylinositol hydrolysis as in Exp 1 (p < 0.05). Progesterone concentrations in incubation medium were increased in response to RU486 and PGF₂α (p < 0.05). Collectively, these data suggest that RU486 and PGF₂α act to stimulate phosphatidylinositol hydrolysis in the mature ovine CL.