Endothelin-1 (ET-1) and tumor necrosis factor-a (TNFa) participate in the cascade of luteolysis. Thus, in the present study the interactions of ET-1 and TNFa with prostaglandin F 2a (PGF 2a ) 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. (1 mmol l 21 ), two consecutive perfusions of ET-1 decreased progesterone release more rapidly. Similarly, a pre-perfusion with PGF 2a followed by consecutive perfusions of ET-1 and then TNFa rapidly decreased progesterone release, with the inhibition most pronounced (35%) at 36 -48 h. The simultaneous infusion of ET-1 with PGF 2a induced a rapid decrease in progesterone release (36% at 36-48 h). In a further study, the possible second messenger systems involved in PGF 2a action on the release of progesterone, OT and ET-1 were investigated. A perfusion with 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 10 mmol l 21 ), A23187 (10 mmol l 21), or PGF 2a 1 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 PGF 2a -primed ovine CL in vivo and thus ET-1 works as a local luteolysin together with PGF 2a during the process of functional luteolysis. During structural luteolysis, TNFa may interact with PGF 2a 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 TNFa interact with PGF 2a as local luteolytic mediators in the ewe as previously suggested.

No abstract