Unique expression and regulatory mechanisms of EG-VEGF/prokineticin-1 and its receptors in the corpus luteum.
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, TNFalpha 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.
Kisliouk
Tatiana
T
Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
Podlovni
Helena
H
Meidan
Rina
R
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003338:Corpus Luteum / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010053:Ovary / Q000098:blood supply / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000737:chemistry / Q000235:genetics*
D012333:RNA, Messenger; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived