Vascular Endothelial Growth Factor is Expressed in Rat Corpus Luteum

Abstract

In the course of the development of the ovarian follicle and differentiation of granulosa cells into corpus luteum (CL), extensive changes in the microvasculature of these structures take place. This suggests the local release of angiogenic factors. In the present work we examined whether a newly described secreted vascular endothelial growth factor (VEGF) is expressed in normal rat ovary by in situ hybridization. Our results demonstrate the expression of VEGF in the CL but not in mural granulosa cells, suggesting a temporal relation between VEGF expression and growth of capillary vessels. The hybridization pattern in the CL was consistent with localization of VEGF message to luteal cells. Expression of VEGF was detected also in cumulus oophorus cells. These findings suggest that VEGF is involved in the process of CL angiogenesis.

Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors.

“…Our failure to demonstrate VPF transcripts in RNA prepared from randomly collected guinea pig ovaries very likely reflects the absence of sufficient numbers of corpora lutea in those ovaries for detection by Northern analysis. We have, however, demonstrated the presence of VPF protein in guinea pig corpus luteum by immunohistochemistry (Sioussat, unpublished data), providing support for and supplementing the findings of Phillips et al (1990).…”

“…Several other tissues were negative, but Northern analysis may be insufficiently sensitive to detect transcripts produced by only a small Molecular Biology of the Cell fraction of cells in a heterologous mixture even if those few cells produce significant levels of transcript. Earlier in situ hybridization experiments (Phillips et al, 1990) described VPF transcription in the corpus luteum but not elsewhere in the ovary, suggesting hormonally regulated cell-specific control of VPF expression. Our failure to demonstrate VPF transcripts in RNA prepared from randomly collected guinea pig ovaries very likely reflects the absence of sufficient numbers of corpora lutea in those ovaries for detection by Northern analysis.…”

“…The protein has several known biological activities, the two best characterized being the abilities to increase vascular permeability and to promote endothelial cell proliferation. Phillips et al (1990) have suggested that the VPF synthesized in the ovary by cells of the corpus luteum might be responsible for inducing the substantial angiogenesis characteristic of this structure. However, angiogenesis is not a feature of normal adult lung, kidney, heart, or adrenal gland, and therefore the presence of readily detectable VPF transcripts in these organs requires another explanation.…”

“…To date, expression of VPF/VEGF has been demonstrated in rodent and human tumor cell lines, in bovine and mouse pituitary-derived cells (Ferrara and Henzel, 1989;Gospodarowicz et al, 1989;Plouet et al, 1989), in rat corpus luteum (Phillips et al, 1990), and recently, in cultured vascular smooth muscle cells (Tischer et al, 1991 (Dvorak et al, 1979) were cultured in DMEM containing 5% calf serum. Guinea pig resident macrophages were harvested from the peritoneal cavity and lungs by flushing with Hanks' balanced salt solution (HBSS).…”

Coordinate expression of vascular endothelial growth factor receptor‐1 (fit‐1) and its ligand suggests a paracrine regulation of murine vascular development

“…Several lines of evidence suggest that vascular endothelial growth factor (VEGF) is a major regulator of physiological blood vessel growth, namely (1) it is a secreted endothelial cell specific mitogen (Ferrara and Henzel, 1989;Gospodarowicz et al, 1989;Plouet et al, 1989), (2) it induces angiogenesis in in vivo test systems (Connolly et al, 1989;Gospodarowicz et al, 1989), and (3) its expression correlates with phases of angiogenesis during embryogenesis and in the female reproductive cycle (Phillips et al, 1990;Breier et al, 1992;Shweiki et al, 1993). The observation that VEGF expression is upregulated in certain tumors, e.g., in glioblastoma (Plate et al, 1992;Shweiki et al, 1992;Phillips et al, 19931, indicated that VEGF may also regulate angiogenesis in tumors.…”