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ANGIOTENSIN II IN THE BOVINE EARLY CORPUS LUTEUM: A POSSIBLE INTERACTION WITH LUTEAL PROSTAGLANDIN F2
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Kobayashi, Shu-ichi1, Berisha, Bajram2, Amselgruber, Werner3, Schams, Dieter2, Miyamoto, Akio1, 1 2 3
ABSTRACT- The newly-formed corpus luteum (CL) rapidly develops after ovulation and has the features of active vascularization and mitosis of steroidogenic cells. These stage-specific mechanisms may contribute to gain the function of prostaglandin F2 (PGF2)-resistant CL at this stage. Recent studies suggest that a vasoactive peptide angiotensin II (Ang II) regulates luteal function. Thus, this study aimed to investigate 1) the production and localization of Ang II, 2) the effects of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on the secretion of Ang II, PGF2, progesterone (P) and oxytocin (OT), and 3) the effects of luteal vasoactive peptides on the secretion of PGF2 and P from bovine early CL, and evaluate a possible interaction of these substances with PGF2. The expression of mRNA for angiotensin-converting enzyme (ACE) was found in theca interna of mature follicle, early CL and endothelial cells (ETC) from developing CL as well as pituitary and kidney, but granulosa cells were negative. The immunohistochemical analysis revealed that blood capillaries (ETC) were stained for ACE, but luteal cells were negative in early CL. To examine the effects of substance on the secretory function of the CL, an in vitro microdialysis system (MDS) was used as a model. The infusion of bFGF and VEGF stimulated Ang II and PGF2 secretion as well as P, but not OT secretion in early CL. The infusion of Ang II after PGF2 infusion continued the stimulatory effect on P release within CL until 3 h thereafter. However, endothelin-1 (ET-1) had no effect on P release. The infusion of Ang II stimulated PGF2 secretion, whereas the infusion of ET-1 did not. In conclusion, the results of this study indicate that the functional angiotensin system exists on the ETC of early CL, and that angiogenic factors upregulate luteal Ang II and PGF2 secretion, which fundamentally supports the mechanism of P secretion in bovine early CL. Supported by grants from JSPS, Novartis foundation, Morinaga Hohshikai, and DFG.
KEY WORDS: angiotensin II, prostaglandin F2, angiogenic growth factors, early CL