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Endocrinology, doi:10.1210/en.2004-1099
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Endocrinology Vol. 146, No. 3 1293-1300
Copyright © 2005 by The Endocrine Society

Role of the Endothelin-1 System in the Luteolytic Process of Pseudopregnant Rabbits

Cristiano Boiti, Gabriella Guelfi, Gabriele Brecchia, Cecilia Dall’Aglio, Piero Ceccarelli, Margherita Maranesi, Chiara Mariottini, Danilo Zampini, Anna Gobbetti and Massimo Zerani

Dipartimento di Scienze biopatologiche veterinarie, Sezione di Fisiologia, Laboratorio di Biotecnologie fisiologiche (C.B., G.G., G.B., M.M., C.M., D.Z.), and Sezione di Anatomia (C.D., P.C.), Università di Perugia, 06126 Perugia, Italy; and Dipartimento di Biologia molecolare, cellulare e animale (A.G., M.Z.), Università di Camerino, 62032 Camerino, Italy

Address all correspondence and requests for reprints to: Dr. Cristiano Boiti, Dipartimento di Scienze biopatologiche veterinarie, Università of Perugia, S. Costanzo 4, 06126 Perugia, Italy. E-mail: cristiano.boiti{at}unipg.it.

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 µg 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 F2{alpha} (PGF2{alpha}). In CL cultured in vitro, ET-1 increased (P ≤ 0.01) both PGF2{alpha} production and luteal nitric oxide synthase activity but decreased (P ≤ 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 ≤ 0.01) at d 9 and 13. ETA-receptor transcript increased (P ≤ 0.01) at d 6, remained at the same level up to d 13, and then declined to the lowest (P ≤ 0.01) levels at d 22. ETB-receptor mRNA increased (P ≤ 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 PGF2{alpha} synthesis from both luteal and accessory cells, via the COX pathways.




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