Production and localisation of angiotensin II in the bovine early corpus luteum: a possible interaction with luteal angiogenic factors and prostaglandin F2 alpha

Abstract

The newly formed corpus luteum (CL) rapidly develops after ovulation and has the features of active vascularisation and mitosis of steroidogenic cells. These stage-specific mechanisms also may contribute to gain the function of prostaglandin F2 (PGF2 )-resistant CL at this stage. Recent studies suggest that the vasoactive peptide angiotensin II (Ang II) regulates luteal function. Thus, this study aimed to investigate (i) the expression of angiotensinconverting enzyme (ACE) mRNA by RT-PCR and the ACE protein expression by immunohistochemistry, (ii) the effects of angiogenic growth factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), on the secretion of Ang II, PGF2 , progesterone and oxytocin (OT), and (iii) the effects of luteal vasoactive peptides (Ang II and endothelin-1 (ET-1)) or OT on the secretion of PGF2 , progesterone and OT from bovine early CL (days 3-4 of the oestrous cycle), and evaluate a possible interaction of these substances with PGF2 . The expression of mRNA for ACE was found in theca interna of mature follicle, early CL and endothelial cells from developing CL as well as pituitary and kidney, but granulosa cells of mature follicle were negative. The immunohistochemical analysis revealed that blood capillaries (endothelial cells) were stained for ACE, but luteal cells were negative in early CL. To examine the effects of substances on the secretory function of the CL, an in vitro microdialysis system was used as a model. The infusion of bFGF and VEGF stimulated Ang II and PGF2 secretion as well as progesterone, but not OT secretion in early CL. The infusion of Ang II after PGF2 infusion continued the stimulatory effect on progesterone and OT release within early CL until 3 h thereafter. However, the infusion of ET-1 alone had no effect on progesterone or OT release. The infusion of luteal peptides such as Ang II and OT stimulated PGF2 secretion, whereas the infusion of ET-1 did not. In conclusion, the overall results of this study indicate that a functional angiotensin system exists on the endothelial cells of early CL, and that angiogenic factors bFGF and VEGF upregulate luteal Ang II and PGF2 secretion, which fundamentally supports the mechanism of progesterone secretion in bovine early CL. This idea supports the concept that the local regulatory mechanism involved in active angiogenesis ensures the progesterone secretion in the developing CL in vivo.

FGF2 is crucial for the development of bovine luteal endothelial networks in vitro

“…VEGFA and FGF2 stimulated progesterone release from microdialysed bovine early CL in vitro (Kobayashi et al 2001). We have also shown previously that progesterone production was increased by the addition of FGF2 with VEGFA in the luteal angiogenesis culture system (Robinson et al 2008).…”

Angiotensin II influences ovarian follicle development in the transgenic (mRen-2)27 and Sprague-Dawley rat

“…In the present study, renin, ANG II and angiotensinogen immunolabelling and ACE binding were detected in both SD and (mRen-2)27 rat corpora lutea. A similar distribution for these RAS components has been reported previously in the rat (Lightman et al 1988, Palumbo et al 1989 and also in human (Palumbo et al 1993) and bovine (Hayashi et al 2000, Kobayashi et al 2001 ovaries. Despite this evidence that some of the components of the RAS are located in corpora lutea, we were unable to detect either renin or angiotensin receptor gene expression, suggesting that renin and ANG II in corpora lutea may be sequestered from blood vessels or neighbouring cells.…”

Vascular composition, apoptosis, and expression of angiogenic factors in the corpus luteum during prostaglandin F2α-induced regression in sheep

“…Determining the profile of angiogenic factors responsible for vascular changes may prove to be important in determining how the composition of the CL is altered during regression. While there are several factors which have been shown to influence vascularity of different tissues, some of the primary regulators of ovarian angiogenesis and vascular function include: the vascular endothelial growth factor (VEGF) system (including the VEGF receptors and the neuropilins; Ferrara et al 1992, Shalaby et al 1995, Neufeld et al 1999, Stacker & Achen 1999, fibroblastic growth factors (FGF) and receptors (Klagsbrun & D'Amore 1991, Neuvians et al 2004a, the angiopoietins (ANGPT) and their receptor Tie-2 (Sato et al 1993, Davis & Yancopoulos 1999, Hazzard et al 2000, Wulff et al 2000, Tanaka et al 2004, the nitric oxide (NO) system (Motta et al 2001, Klipper et al 2004, Shi et al 2004, Al-Gubory et al 2005, and the renin-angiotensin system (Hansel & Blair 1996, Hayashi & Miyamoto 1999, Kobayashi et al 2001. While it is most certain that there are several other angiogenic factors playing a role in the regulation of vascular function, selected members from these families were investigated in the current experiment.…”