Role of the 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 microg 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 ET(A)/ET(B) receptor antagonist, or cyclooxygenase (COX) inhibitor blocked the luteolytic action of ET-1 but not that induced by prostaglandin F2alpha (PGF2alpha). In CL cultured in vitro, ET-1 increased (P </= 0.01) both PGF(2alpha) production and luteal nitric oxide synthase activity but decreased (P < or = 0.01) progesterone release. Addition of ET(A) 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 < or = 0.01) at d 9 and 13. ET(A)-receptor transcript increased (P < or = 0.01) at d 6, remained at the same level up to d 13, and then declined to the lowest (P < or = 0.01) levels at d 22. ET(B)-receptor mRNA increased (P < or = 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 PGF2alpha synthesis from both luteal and accessory cells, via the COX pathways.
Boiti
Cristiano
C
Dipartimento di Scienze biopatologiche veterinarie, Sezione di Fisiologia, Laboratorio di Biotecnologie fisiologiche, Università of Perugia, S. Costanzo 4, 06126 Perugia, Italy. cristiano.boiti@unipg.it
Guelfi
Gabriella
G
Brecchia
Gabriele
G
Dall'Aglio
Cecilia
C
Ceccarelli
Piero
P
Maranesi
Margherita
M
Mariottini
Chiara
C
Zampini
Danilo
D
Gobbetti
Anna
A
Zerani
Massimo
M
D000818:Animals; D015153:Blotting, Western; D000077300:Bosentan; D003338:Corpus Luteum / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D015237:Dinoprost / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011374:Progesterone / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D017931:DNA Primers; D019332:Endothelin-1; D012333:RNA, Messenger; D013449:Sulfonamides; D011374:Progesterone; D012313:RNA; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D000077300:Bosentan