Prostaglandin F2α promotes the inhibitory action of endothelin-1 on the bovine luteal function in vitro

Abstract

Prostaglandin F2 alpha (PGF2 alpha) is a primary luteolysin in the cow. Although the mechanisms involved in luteolysis are thought to be a complex of its direct action on luteal cells and indirect effect on luteal blood flow, the detailed mechanisms remain to be elucidated. This study focuses on the possible interaction of endothelial cells-derived endothelin-1 (ET-1) with PGF2 alpha in the rapid suppression of progesterone release from the bovine corpus luteum (CL). In in vitro microdialysis system (MDS) of CL, PGF2 alpha acutely stimulated the release of progesterone and oxytocin during infusion and ET-1 release after infusion. Moreover, PGF2 alpha induced slight decrease of progesterone release during the last period of the experiment (8-11 h after PGF2 alpha exposure). Two 1 h-perfusions of ET-1 at 3 h intervals induced only a slight decrease of progesterone release after the second perfusion. This treatment also affected the oxytocin release; the first ET-1 perfusion produced an acute stimulation, whereas the second ET-1 perfusion inhibited the release to below 50%. When the CL pieces were pre-perfused with PGF2 alpha for 2 h, the two consecutive perfusion of ET-1 at 3 h intervals induced drastic decrease in progesterone and oxytocin release only after the second ET-1 perfusion. Thus, a pre-exposure with PGF2 alpha clearly potentiated the inhibiting activity of ET-1 in the progesterone release. These results suggest a physiological impact of PGF2 alpha and ET-1 in the rapid cascade of functional luteolysis in vivo, and a possible interaction between endothelial cells and luteal cells.

Direct Effect of PGF2.ALPHA., TPA and lonophore A23187 on Progesterone Release from Microdialyzed Corpus Luteum inthe Cow.

“…This may imply that a calcium influx into cytoplasm by A23187 and an intracellular calcium release from intracellular organelles by PGF2α additively induced hyper-activation of intracellular Ca 2+ , resulting in a pronounced P inhibition followed by the start of cell death. This concept of functional luteolysis (P decrease) on the basis of hyper-activation of intracellular Ca 2+ is supported by our recent observation [17]. Namely, pre-exposure of the microenvironment within the bovine mid-CL with PGF2α potentiated the P inhibiting activity of endothelin-1 (ET-1) in the in vitro MDS model, which involves the activation of intracellular Ca 2+ .…”

“…Namely, pre-exposure of the microenvironment within the bovine mid-CL with PGF2α potentiated the P inhibiting activity of endothelin-1 (ET-1) in the in vitro MDS model, which involves the activation of intracellular Ca 2+ . Consequently, we and others have proposed that a vasoactive peptide such as ET-1 mediates luteolytic actions of PGF2α in the bovine CL [17][18][19]. Recently, we have found that angio- tensin II is a possible additive luteolytic mediator in the bovine CL [20].…”

Immunoreactivity for Gonadotropin-Releasing Hormone in Microdialyzed Perfusates of Bovine Mature Follicles In Vitro.

“…Particularly, we previously showed that infusion of LH clearly increased the release of E 2 in this system [15]. The transfer capacity of the membrane was estimated to be 1% for steroids and prostaglandins, and 0.1% for peptides and LH [17,18], when it was determined as described earlier [19]. The solutions were then infused into the MDS for 2 h (LH between 4-6 h; ET-1, TNFα or IL-β between 8-10 h).…”

“…BSA was added to the samples to a final concentration of 1 mg/ml. The samples were then applied to a Sep-Pak C 18 Cartridge (Waters, Millford, MA, USA) as described previously [18]. The eluted residue was evaporated and then dissolved in 200 µl assay buffer (42 mM Na2HPO4, 8 mM KH2PO4, 20 mM NaCl, 4.8 mM EDTA, 0.05% BSA, pH 7.5) for peptide EIA.…”

Intraluteal Release of Progesterone and Prostaglandins during PGF2.ALPHA.-Induced Luteolysis in Ewes: Local Effects of Tumor Necrosis Factor-.ALPHA..

“…These findings strongly suggest that the invasion of immune cells into the regressing CL is the major reason for the increase of TNF-α concentration in the CL at this period. Recently, we and others have shown that the production and release of endothelin-1, a vasoconstrictive peptide originated from endothelial cells, increased in the CL and ovarian venous plasma ipsilateral to the CL from 2 h after PGF2α injection in the cow, and proposed that endothelin-1 interacts with PGF2α as a local luteolytic factor [21][22][23][24]. It is likely that such vasoconstrictive peptides are responsible for an acute response to luteolytic PGF2α in both 1) direct inhibition of P release and 2) a vasoconstriction of arterioles, and thereby they can start an acute depletion of P release followed by a degeneration of CL tissue in which TNF-α plays a major role.…”