Endothelin-1 mediates prostaglandin F-2 alpha-induced luteal regression inthe ewe

A diversified series of experiments was conducted to determine the potentia l role of endothelin-1 (ET-1) in ovine luteal function. Endothelin-1 inhibi ted basal and LH-stimulated progesterone production by dispersed ovine lute al cells during a 2-h incubation. This inhibition was removed when cells we re preincubated with cyclo-D-Asp-Pro-D-Val-Leu-D-Trp (BQ123), a highly spec ific endothelin ETA receptor antagonist. Administration of a luteolytic dos e of prostaglandin F-2 alpha (PGF(2 alpha)) rapidly stimulated gene express ion for ET-1 in ovine corpora lutea (CL) collected at midcycle, Intraluteal administration of a single dose of BQ123 to ewes on Day 8 or 9 of the estr ous cycle mitigated the luteolytic effect of PCF2 alpha. Intramuscular admi nistration of 100 mug ET-1 to ewes at midcycle reduced plasma progesterone concentrations for the remainder of the estrous cycle. Following pretreatme nt with a subluteolytic dose of PCF2 alpha/ i.m. administration of 100 mug ET-1 caused a rapid decline in plasma progesterone and shortened the length of the estrous cycle, These data complement and extend previously publishe d reports in the bovine CL and are the strongest evidence presented to date in support of a role for ET-1 in PGF(2 alpha)-mediated luteal function in domestic ruminants.