Regulation of Endothelin-1 Expression in the Bovine Corpus Luteum: Elevation by Prostaglandin F_2α

Prostaglandin F_2α (PGF_2α) has been recognized as the physiological luteolysin in ruminants and other species for more than three decades; however, the mechanisms involved in its action are poorly understood. We previously have shown that endothelin-1 (ET-1) mediates, at least in part, the action of PGF_2α, and the current study examines the effect of PGF_2α on the expression of ET-1 in bovine corpus luteum (CL). Endothelins (ETs) were extracted from CL, collected at various times of the estrous cycle, and highest levels were found during luteolysis. The expression of prepro-ET-1 was also highest in regressing CL, suggesting that PGF_2α may have elevated ET-1 expression. This was confirmed by demonstrating that administration of PGF_2α to heifers at midcycle elevated luteal ET-1 expression. Levels were induced as soon as 2 h after PGF_2α treatment and 24 h later were 7-fold higher than preinjection levels. Endothelial cells isolated from bovine CL produced ET-1, and addition of PGF_2α, oxytocin (OT), and vasopressin-augmented ET biosynthesis. Induction of ET-1 expression by PGF_2α in these cells was evident after a short incubation time (15-90 min). Taken together, these data suggest that stimulation of luteal ET-1 expression by PGF_2α may be achieved by several nonmutually exclusive mechanisms: 1) by acting directly on luteal endothelial cells; 2) indirectly, via OT release from large luteal cells; and 3) by causing hypoxia in the CL (as a result of ET-1-induced vasoconstriction). The latter mechanism may serve to augment ET-1 secretion in a positive-feedback process.