Real-time relationships between intraluteal and plasma concentrations of endothelin, oxytocin, and progesterone during prostaglandin F2alpha-induced luteolysis in the cow.

Recent observations suggest that the endothelial cell-derived vasoconstrictive peptide endothelin-1 (ET-1) interacts with prostaglandin F2alpha (PGF2alpha) and that luteal ET-1 participates in the rapid cascade of functional luteolysis in vivo. Thus, the present study aimed to determine in detail the real-time changes in ET-1, oxytocin (OT), and progesterone (P4) concentrations within the regressing corpus luteum (CL), along with the changes in ovarian venous plasma (OVP) ipsilateral to the CL as well as in jugular venous plasma (JVP) in the cow. In the first study, peripheral plasma from daily sampling during the estrous cycle (n = 6) showed clear changes in ET-1 concentration with the stage of the cycle (p < 0.05). ET-1 remained at basal concentrations (23.2+/-1.3 pg/ml) on Days 2-12, increased (p < 0.05) on Days 13-19 (33.5+/-2.6 pg/ml), and reached the highest (p < 0.001) concentrations (45.6+/-4.4 pg/ml) on Days 20-22 after estrus. These data indicate that plasma ET-1 concentration increases around luteolysis and estrus. In the second study, a microdialysis system (MDS) was surgically implanted into the CL of 11 cows in the midluteal phase. In 4 of the 11 cows, the catheter was also fitted to the ovarian vein ipsilateral to the CL at surgery. A PGF2alpha analogue (cloprostenol; 500 microg) was then injected (designated as 0 h) i.m. to induce luteolysis. In the cows fitted with an MDS, the PGF2alpha injection clearly induced a rapid decrease in intraluteal P4 release within 4 h (p < 0.05), and the levels decreased to 20% of the baseline after 24 h. Intraluteal release of ET-1 increased (p < 0.05) to 160% within 4 h after PGF2alpha injection, when an enormous OT release (to 950%) occurred, which reached a plateau of 250% after 20 h that persisted until 72 h. ET-1 release into the ovarian vein began to increase at 2 h after PGF2alpha injection, when the acute OT release almost dropped to the baseline. The ET-1 concentration was temporarily (between 0 and 24 h after PGF2alpha) 2-3 times higher in OVP than in JVP (p < 0.05), and increased again to higher levels than in JVP from 32 to 64 h (p < 0.05). ET-1 concentrations in JVP gradually increased from 10 pg/ml to 30 pg/ml during PGF2alpha-induced luteolysis (p < 0.05). In conclusion, PGF2alpha injection rapidly increased ET-1 release within the regressing CL as well as into the ovarian venous blood in the cow. The overall results strongly support the hypothesis that luteal ET-1 is a local luteolytic mediator/promotor in the regressing bovine CL.