Kisliouk, T., Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
Levy, N., Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
Hurwitz, A., Dept. of Obstetrics and Gynecology, Hadassah University Hospital, Jerusalem 91905, Israel
Meidan, R., Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel

Endocrine gland vascular endothelial growth factor (EG-VEGF) is a novel angiogenic mitogen selective for endothelial cells (EC) in endocrine glands. EG-VEGF is identical to a protein previously cloned and termed prokineticin (PK)-1. The present study examined the expression of EG-VEGF/PK-1 and its receptors in ovarian steroidogenic cells and EC and compared the regulation of EG-VEGF/PK-1 and VEGF expression in SV40 transformed luteinized human granulosa cell line (SVOG). Normal granulosa or SVOG cells expressed EG-VEGF/PK-1 mRNA. Incubation of SVOG cells with forskolin augmented EG-VEGF/PK-1 expression in a dose-dependent manner. Chemical hypoxia induced by CoCl2 and desferrioxamine mesylate (100 μM each) markedly reduced EG-VEGF/PK-1. In contrast, hypoxia significantly elevated VEGF mRNA (VEGF165, 189) and protein secretion. Thrombin, like hypoxia, also induced an opposite effect on VEGF and EG-VEGF/PK-1. Whereas EG-VEGF/PK-1 and VEGF were inversely regulated, steroidogenesis and EG-VEGF/PK-1 were positively correlated in SVOG cells. A distinct pattern of ovarian PK receptor (PK-R) expression was observed in which steroidogenic cells predominantly express PK-R1 receptors, whereas corpus luteum-derived EC express high levels of both PK-R1 and PK-R2. Therefore, acting via either PK-R2 or PK-R1, EG-VEGF/PK-1 may have angiogenic as well as nonangiogenic functions in the ovary.