Presence and regulation of endocrine gland vascular endothelial growth factor/prokineticin-1 and its receptors in ovarian cells.
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 CoCl(2) and desferrioxamine mesylate (100 micro M 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.
Kisliouk
Tatiana
T
Department of Animal Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
Levy
Nitzan
N
Hurwitz
Arye
A
Meidan
Rina
R
D043925:Angiogenesis Inducing Agents / Q000096:biosynthesis*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D004702:Endocrine Glands / Q000378:metabolism*; D005260:Female; D005768:Gastrointestinal Hormones / Q000096:biosynthesis*; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013917:Thrombin / Q000494:pharmacology; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived
D043925:Angiogenesis Inducing Agents; D005768:Gastrointestinal Hormones; C467610:PROK1 protein, human; D012333:RNA, Messenger; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; D005576:Colforsin; D011374:Progesterone; D040262:Receptors, Vascular Endothelial Growth Factor; D013917:Thrombin