Is endothelin-1 luteolytic or antiluteolytic in ewes?

Endothelin-1 (ET-1) has been reported to mediate prostaglandin (PG) F2α (PGF2α)-induced luteolysis. Prostaglandins E (PGE; PGE1 + PGE2) are associated with implantation, maternal recognition of pregnancy, and are antiluteolytic and luteotropic in vitro and in vivo. ET-1 increased PGE secretion by bovine luteal tissue in vitro from cows where estrus was not synchronized or when estrus was synchronized with lutalyse and did not affect luteal PGF2α or progesterone secretion, which does not support the concept that ET-1 is luteolytic or mediates PGF2α luteolysis. Therefore, the objective of this experiment was to determine whether ET-1 infused every 6 h from 2400 h on day 10-1800 h on day 18 of the ovine estrous cycle either into the interstitial tissue of the ovarian vascular pedicle (IP) or intrauterine (IU) adjacent to the luteal-containing ovary was luteolytic in ewes. Treatments were: Vehicle-IP; Vehicle-IU; ET-1-IP; or ET-1-IU. Weights of corpora lutea differed (P ≤ 0.05) among treatment groups. Weights of corpora lutea at 1800 h on day 18 were: VEH-IP-247 ± 38 mg; VEH-IU-195 ± 31 mg; ET-1-IP-626 ± 74 mg; and ET-1-IU-542 ± 69 mg. Luteal weights on day 18 in ET-1-IP or ET-1-IU-treated ewes did not differ (P ≥ 0.05), but were heavier (P ≤ 0.05) than in the Vehicle-IP or Vehicle-IU treatment groups which did not differ (P ≥ 0.05). Profiles of progesterone in jugular venous plasma of both control groups treated with Vehicle-IP or Vehicle-IU were lower (P ≤ 0.05) than in ewes treated with ET-1-IP or ET-1-IU, which did not differ (P ≥ 0.05) between ET-1-IP or ET-1-IU treatment groups. Treatment with ET-1-IP or ET-1-IU increased (P ≤ 0.05) the PGE:PGF2α ratio when compared to the Vehicle-IP or Vehicle-IU treatment groups, which did not differ (P ≥ 0.05) between each other. In summary, ET-1 prevented the decrease in luteal weights and the decline in progesterone, but increased the PGE:PGF2α ratio when compared to controls. Therefore, it is concluded that ET-1 is not luteolytic in ewes, but instead may be luteotropic or antiluteolytic by altering uterine secretion of the PGE:PGF2α ratio, since PGE1 or PGE2 are luteotropic in vitro and in vivo, PGE1 or PGE2 prevent PGF2α-induced luteolysis in vitro and in vivo, and PGE1 and PGE2 increase two-fold in ewe endometrium to prevent luteolysis during early pregnancy.