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Angiotensin II Interacts with Prostaglandin F₂ and Endothelin-1 as a Local Luteolytic Factor in the Bovine Corpus Luteum In Vitro¹

^a Department of Animal Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan

Recent findings suggest that the ovarian renin-angiotensin system may regulate ovarian function through the paracrine/autocrine actions of angiotensin II (Ang II). In this study, we have examined and characterized the local effects of Ang II as a luteolytic factor and its interaction with prostaglandin F₂ (PGF₂) and endothelin-1 (ET-1) in the bovine corpus luteum (CL) of the mid-luteal phase, by using an in vitro microdialysis system (MDS). Ang II was detected in the MDS perfusate (4 pg/ml), and infusion of PGF₂ (10^-6 M) for 2 h increased the Ang II release by 50–100% during the following experimental period, in addition to its stimulation of ET-1 release. Two 2-h infusions of Ang II (10^-7-10^-5 M) separated by a 2-h interval induced a dose- and time-dependent decrease of progesterone (P₄) release by 41–66%. When the luteal explants were pre-perfused with PGF₂ (10^-6 M) for 2 h, two consecutive perfusions of Ang II (10^-6 M) at a 2-h interval rapidly reduced the P₄ release (by 50%). This reduction occurred 6 h earlier than those of infusions of PGF₂ or Ang II alone. The simultaneous infusion of either 1) Ang II (10^-6 M) with PGF₂ (10^-6 M), 2) ET-1 (10^-7 M) with PGF₂, or 3) Ang II + ET-1 with PGF₂ (10^-6 M) for 2 h also induced a rapid and pronounced (60%) decrease in P₄ release. Perfusion with the Ang II antagonist blocked the P₄-suppressing activity of Ang II alone or PGF₂ + Ang II infusion. Ang II stimulated the release of ET-1 and oxytocin during infusion but inhibited them after infusion.

These results show that Ang II is released in the bovine midcycle CL in vitro, and this peptide, either alone or together with PGF₂, can suppress the release of P₄. As PGF₂ directly stimulated Ang II release, Ang II may influence the critical period for starting the cascade of functional luteolysis in vivo and might lead to structural luteolysis with ET-1 as a major vasoconstrictor. The overall results suggest that Ang II may have an important role at luteolysis in the bovine CL.

¹ This study was supported by the Japan-Germany joint research project of the Japan society for the Promotion of Science.

² Correspondence. FAX: 81 155 49 5462; akiomiya{at}obihiro.ac.jp

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