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This version published online on December 9, 2004
Endocrinology, doi:10.1210/en.2004-1099
A more recent version of this article appeared on March 1, 2005
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Submitted on August 20, 2004
Accepted on November 30, 2004

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 (CB, GG, GB, MM, CM, DZ), and Sezione di Anatomia (CDA, PC), Università di Perugia, Italy, and Dipartimento di Biologia molecolare, cellulare e animale (AG, MZ), Università di Camerino, Camerino, Italy

* To whom correspondence should be addressed. 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 controlling the corpora lutea (CL) life span in rabbits. ET-1 (10 µg iv) administration at days 9 and 12 of pseudopregnancy induced a functional luteolysis within 24 h of injection, but it was ineffective at both days 4 and 6. Pre-treatments 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 (PG) F2{alpha}. In CL cultured in vitro, ET-1 increased (P ≤ 0.01) both PGF2{alpha} production and luteal nitric oxide (NO) synthase (NOS) 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 size in day-9 CL. Up to day 6 of pseudopregnancy, ET-1 mRNA abundance in CL was poorly expressed, but then increased (P ≤ 0.01) at days 9 and 13. ETA-receptor transcript increased (P ≤ 0.01) at day 6, remained at the same level up to day 13, and then declined to the lowest (P ≤ 0.01) levels at day 22. ETB-receptor mRNA increased (P ≤ 0.01) throughout the late-luteal stage from day 13 up to day 18. Our data suggest that the luteolytic action of ET-1 may be due to PGF2{alpha} synthesis from both luteal and accessory cells, via the COX pathways.
Key words: ET-1 • ETA-R • ETB-R • NO • luteolysis • PGF2{alpha} • corpus luteum • rabbit




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