Role of endothelin-1 system in the luteolytic process of pseudopregnant rabbits

The aim of this study was to better understand the role of the endothelin-1 (ET-1) system in the process of controlling the corpora lutea (CL) life span in rabbits. ET-1 (10 mug iv) administration at d 9 and 12 of pseudopregnancy induced a functional luteolysis within 24 h of injection, but it was ineffective at both d 4 and 6. Pretreatments with Bosentan, a dual ETA/ETB receptor antagonist, or cyclooxygenase ( COX) inhibitor blocked the luteolytic action of ET-1 but not that induced by prostaglandin F-2alpha (PGF(2alpha)). In CL cultured in vitro, ET-1 increased (P less than or equal to 0.01) both PGF(2alpha) production and luteal nitric oxide synthase activity but decreased (P less than or equal to 0.01) progesterone release. Addition of ETA receptor antagonist BQ123 or COX inhibitor blocked the ET-1 luteolytic effects. Positive staining for ET-1 receptors was localized in ovarian blood vessels, granulosa cells of large follicles, and luteal cells. Immunoblot analysis of ET-1 receptor protein revealed a strong band of approximately 48 kDa in d-9 CL. Up to d 6 of pseudopregnancy, ET-1 mRNA abundance in CL was poorly expressed but then increased (P less than or equal to 0.01) at d 9 and 13. ETA-receptor transcript increased (P less than or equal to 0.01) at d 6, remained at the same level up to d 13, and then declined to the lowest (P less than or equal to 0.01) levels at d 22. ETB-receptor mRNA increased (P less than or equal to 0.01) throughout the late-luteal stage from d 13 up to d 18. Our data suggest that the luteolytic action of ET-1 may be a result of PGF(2alpha) synthesis from both luteal and accessory cells, via the COX pathways.