Is endothelin-1 luteolytic or antiluteolytic in ewes?

Abstract Endothelin-1 (ET-1) has been reported to mediate prostaglandin (PG) F 2 α (PGF 2 α)-induced luteolysis. Prostaglandins E (PGE; PGE 1  + PGE 2 ) 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 PGF 2 α or progesterone secretion, which does not support the concept that ET-1 is luteolytic or mediates PGF 2 α 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:PGF 2 α 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:PGF 2 α 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:PGF 2 α ratio, since PGE 1 or PGE 2 are luteotropic in vitro and in vivo , PGE 1 or PGE 2 prevent PGF 2 α-induced luteolysis in vitro and in vivo , and PGE 1 and PGE 2 increase two-fold in ewe endometrium to prevent luteolysis during early pregnancy.