A cooperative action of endothelin-1 with prostaglandin F2α on luteal function in the cow

Prostaglandin F2α (PGF2α) is the primary luteolysin in the cow, and luteal endothelin-1 (ET-1) interacts with PGF2α during the process of luteolysis. In contrast, a developing corpus luteum (CL) is refractory to exogenous administration of PGF2α. Thus, the present study was aimed to investigate the functional relationship between ET-1 and PGF2α in the mid-CL (PGF2α-sensitive) and early-CL (PGF2α-refractory). In the mid-CL model, cows (n=6/treatment) were assigned to receive one of five types of treatments on day 10 of the estrous cycle: (1) an injection of saline; control, (2) a 500μg of PGF2α analogue (sufficient dose to induce luteolytis); full-PG, (3) an intraluteal injection of 0.25mg ET-1; ET-1, (4) a 125μg of PGF2α (insufficient dose to induce luteolytis); 1/4PG or (5) an intraluteal injection of 0.25mg ET-1 after administration of a insufficient dose of PGF2α analogue; 1/4PG/ET. In the early-CL model, cows were assigned to receive one of two types of treatments on day 5 of the estrous cycle: (1) a sufficient dose of PGF2α analogue; PG (n=5) or (2) an intraluteal injection ET-1 after a sufficient dose of PGF2α; PG/ET (n=7). In the mid-CL model, 1/4PG/ET resulted in a rapid reduction of progesterone (P) concentrations similar to that in full-PG from the next day. However, the levels of P in 1/4PG/ET (1.5–2.5ng/ml) kept significantly higher than that in full-PG (<0.5ng/ml). ET-1 or 1/4PG did not decrease plasma P concentrations (4–6ng/ml). The plasma ET-1 levels increased with the full-PG administration. In the early-CL model, both treatments had no effect on plasma P increase and ET-1 levels. The overall results indicate that the intraluteal ET-1 injection after administration of insufficient dose of PGF2α induces the depression of P secretion in vivo during the mid luteal phase in the cow, supporting the concept that ET-1 is one of a local mediator of functional luteolysis in the cow. The result further indicates that the early-CL is not only PG-refractory but also ET-1-refractory.