EXPRESSION OF VASCULAR-PERMEABILITY FACTOR VASCULAR ENDOTHELIAL GROWTH-FACTOR BY HUMAN GRANULOSA AND THECA LUTEIN CELLS - ROLE IN CORPUS-LUTEUM DEVELOPMENT

Vascular permeability factor/vascular endothelial growth factor (VPF/V EGF) is a cytokine that is overexpressed in many tumors, in healing wo unds, and in rheumatoid arthritis, VPF/VEGF is thought to induce angio genesis and accompanying connective tissue stroma in two ways: 1), by increasing microvascular permeability, thereby modifying the extracell ular matrix and 2), as an endothelial cell mitogen VPF/VEGF has been r eported in animal corpora lutea and we investigated the possibility th at it might be present in human ovaries and have a role in corpus lute um formation, We here report that VPF/VEGF mRNA and protein are expres sed by human ovarian granulosa and theca cells late in follicle develo pment and, subsequent to ovulation, by granulosa and theca lutein cell s, Therefore, VPF/VEGF is ideally positioned to provoke the increased permeability of thecal blood vessels that occurs shortly before ovulat ion. VPF/VEGF likely also contributes to the angiogenesis and connecti ve tissue stroma generation that accompany corpus luteum/corpus albica ns formation. Finally, VPF/VEGF was overexpressed in the hyperthecotic ovarian stroma of Stein-Leventhal syndrome in which it may also have a pathophysiological role.