Co-Authors:
Kisliouk, T., Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel
Podlovni, H., Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel
Meidan, R., Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel
Abstract:
Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) or Prokineticin-1 (PK-1) is a novel cysteine-rich protein that belongs to the AVIT protein family. EG-VEGF/PK-1, described as selective angiogenic mitogen, is widely expressed in different tissues including steroidogenic endocrine glands. This review summarizes the expression and functions of EG-VEGF/PK-1 in corpus luteum (CL)-derived cells: endothelial and steroidogenic cell types. EG-VEGF/PK-1 mRNA is expressed by luteal steroidogenic cells of human, rat and bovine ovaries, but was absent from the luteal Endothelial cells CLEC. Luteal EC expressed high levels of both PK-receptors PK-R1 and PK-R2 - the two G protein-coupled PK-1 receptors. Interestingly, expression of EG-VEGF/PK-1 and VEGF were inversely regulated in human and bovine luteinized granulosa cells. EG-VEGF/PK-1 elevated [3H]-thymidine incorporation, MAPK activation and c-jun/fos mRNA expression and enhanced LEC proliferation. EG-VEGF/PK-1 also inhibited serum starvation-induced apoptosis in these cells. Stress conditions such as serum withdrawal, TNFα and chemical hypoxia markedly increase PK-R2 expression, whereas mRNA levels of PK-R1 remain unchanged, implying that the anti-apoptotic effect of PK-1 on LEC may be mediated via PK-R2. Besides its direct mitogenic and anti-apoptotic effects, EG-VEGF/PK-1 elevated VEGF mRNA expression in bovine luteal steroidogenic cells, which possesses only PK-R1. Together, these findings suggest an important role for PK-1 in luteal function by acting as a mitogen and survival factor in LEC. Nevertheless, the inverse regulation of EG-VEGF/PK1 and VEGF mRNA expression by ovarian cells and the distribution of its receptors may suggest that in addition to its angiogenic effects, EG-VEGF/PK-1 may also play other roles in ovary. © 2005 Elsevier GmbH. All rights reserved.