VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) VASCULAR-PERMEABILITY FACTOR (VPF) PRODUCTION BY LUTEINIZED HUMAN GRANULOSA-CELLS IN-VITRO - A PARACRINE SIGNAL IN CORPUS-LUTEUM FORMATION

Vascularization is a prerequisite for corpus luteum formation. Angioge nesis is thought to be regulated by vascular growth factors. Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) sp ecifically induces endothelial cell proliferation as well as angiogene sis and increases capillary permeability. Recently, VEGF/VPF-mRNA expr ession was demonstrated in luteinized human granulosa cells (GC) in vi tro. In addition, the production of VEGF/VPF by human granulosa can be demonstrated immunocytochemically. VEGF/VPF is thought to mediate its effects through specific cell surface receptors. So far, two VEGF/VPF -receptors (VEGF/VPF-R) have been identified (KDR, and flt-1). A third receptor (flt-4) is highly correlated to KDR and flt-1, but the true ligand for this receptor is still unknown. The appearance of all three receptors is move or less restricted to endothelial cells. To clarify whether VEGF/VPF acts in an auto- or paracrine fashion in human lutei nized GC, mRNA was scrutinized for specific expression of the three re ceptors by Northern blot technique. No specific VEGF/VPF-R or flt-4 tr anscripts were detectable, indicating that VEGF/VPF is a genuine parac rine growth factor from human luteinized GC directed to endothelial ce lls.