Local interaction of prostaglandin F2α with endothelin-1 and tumor necrosis factor-α on the release of progesterone and oxytocin in ovine corpora lutea in vivo: a possible implication for a luteolytic cascade

Endothelin-1 (ET-1) and tumor necrosis factor-α (TNFα) participate in the cascade of luteolysis. Thus, in the present study the interactions of ET-1 and TNFα with prostaglandin F2α (PGF2α) on the release of progesterone and oxytocin (OT) within the corpus luteum (CL) were investigated. A microdialysis system (MDS) was surgically implanted in ovine CL (one MDS line/CL; 5–10 lines/ewe) formed after super-ovulation. A 4-h perfusion with PGF2α (0.01–1 μmol l −1) induced no clear effect on progesterone release, but acutely stimulated OT release in a dose-dependent manner. A perfusion of PGF2α (1 μmol l −1) increased ET-1 release over a period of 12 h. Two perfusions of ET-1 (0.1 μmol l−1) or a perfusion of ET-1 followed by TNFα (200 ng ml−1) decreased progesterone release (56–64% at 36–48 h). When the CL were pre-perfused with PGF2α (1 μmol l−1), two consecutive perfusions of ET-1 decreased progesterone release more rapidly. Similarly, a pre-perfusion with PGF2α followed by consecutive perfusions of ET-1 and then TNFα rapidly decreased progesterone release, with the inhibition most pronounced (35%) at 36–48 h. The simultaneous infusion of ET-1 with PGF2α induced a rapid decrease in progesterone release (36% at 36–48 h). In a further study, the possible second messenger systems involved in PGF2α action on the release of progesterone, OT and ET-1 were investigated. A perfusion with 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 10 μmol l−1), A23187 (10 μmol l−1), or PGF2α + A23187 increased progesterone release during infusion, but decreased it after perfusion. All treatments induced a massive release of OT during infusion, and increased ET-1 release after infusion. These results show that ET-1 is capable of suppressing progesterone release in the PGF2α-primed ovine CL in vivo and thus ET-1 works as a local luteolysin together with PGF2α during the process of functional luteolysis. During structural luteolysis, TNFα may interact with PGF2α and ET-1 to cause a rapid drop in progesterone release and accelerate the process of luteolysis. This result supports the contention that ET-1 and TNFα interact with PGF2α as local luteolytic mediators in the ewe as previously suggested.