Production and binding of endothelin-2 (EDN2) in the rat ovary: endothelin receptor subtype A (EDNRA)-mediated contraction
Phillip J. Bridges A , Misung Jo B , Linah Al Alem A , Giyoun Na A , Wen Su C , Ming C. Gong C , Myoungkun Jeoung A and CheMyong Ko A D EA Division of Clinical and Reproductive Sciences, University of Kentucky, Lexington, KY 40536, USA.
B Department of Obstetrics and Gynecology, University of Kentucky, Lexington, KY 40536, USA.
C Department of Physiology, University of Kentucky, Lexington, KY 40536, USA.
D Department of Biology, University of Kentucky, Lexington, KY 40536, USA.
E Corresponding author. Email: cko2@uky.edu
Reproduction, Fertility and Development 22(5) 780-787 https://doi.org/10.1071/RD09194
Submitted: 18 August 2009 Accepted: 11 November 2009 Published: 7 April 2010
Abstract
Endothelin-2 (EDN2)-mediated contraction has been proposed as a final mechanical signal facilitating ovulation. The objectives herein were to determine (1) whether ovarian endothelins were increased before ovulation; (2) whether a specific endothelin-converting enzyme (ECE) was mediating their production; (3) which receptor was facilitating ovarian contraction; and (4) whether receptor-specific antagonism affected ovulation. Follicular development was induced in immature rats with 10 IU pregnant mare serum gonadotrophin (PMSG) and the ovulatory cascade was initiated 48 h later with 10 IU human chorionic gonadotrophin (hCG). In Experiment 1, an immunoassay revealed that the ovarian concentration of endothelin peptide was increased 7-fold 12 h after hCG when compared with 48 h after PMSG (P < 0.05). In Experiment 2, real-time PCR indicated that mRNA for Ece1, but not Ece2, was increased in granulosa cells collected 12 h after hCG when compared with those collected before the ovulatory stimulus (P < 0.05). In Experiment 3, isometric tension analysis revealed that the contractile effect of EDN2 was mediated by endothelin receptor A (EDNRA), not B (EDNRB). In Experiment 4, no effect was observed on the rate of ovulation when rats were treated with an antagonist specific to EDNRA (BQ123) or EDNRB (BQ788), or when mice were treated with BQ123, BQ788 or BQ123 + BQ788. In conclusion, endothelin peptide is produced before ovulation and the contractile action of EDN2 within the ovary is facilitated via EDNRA. In addition, findings of this study indicate synergistic interactions among contractile factors affect ovulatory outcome, while the role of EDNRB alone in the process of ovulation requires further investigation.
Additional keywords: constriction, ovulation, rupture.
Acknowledgements
This work was supported by grant RO1HD052694 (C.K.), K12 DA014040 (P.B.) and P20 RR15592 (P.B. and C.K.) from the National Institutes of Health.
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