VASCULAR ENDOTHELIAL GROWTH-FACTOR IN PRIMATE ENDOMETRIUM IS REGULATED BY ESTROGEN-RECEPTOR AND PROGESTERONE-RECEPTOR LIGANDS IN-VIVO

We investigated hormonal regulation of endometrial angiogenesis in men struating primates. This study was designed to demonstrate: (i) that c ell-specific vascular endothelial growth factor (VEGF) production and expression in monkey endometrium are regulated by steroid receptor lig ands; and (ii) mifepristone (RU 486) alters VEGF production even in th e absence of a progestin agonist. Endometrial VEGF production was comp ared by computer-assisted immunohistochemical analysis during induced hypoestrogenism and after oestradiol, progestin, or antiprogestin (mif epristone) treatment. VEGF gene expression was estimated by quantitati ve reverse-transcriptase polymerase chain reaction (RT-PCR) in endomet rial samples from castrate cynomolgus monkeys, from intact monkeys in the luteal phase, and from monkeys treated for 20 days with levonorges trel (LNG) or mifepristone. VEGF staining intensities in glandular epi thelium and VEGF mRNA expression were highest in hypoestrogenic monkey s. Progestin treatment induced intense VEGF staining in the stroma. Ge ne expression of VEGF-189, but not other isoforms, was higher in proge sterone- and progestin (LNG)-exposed endometria compared to mifepristo ne-exposed endometria or endometria from anovulatory cycles (P < 0.04) . Mifepristone abolished VEGF staining in glandular epithelium almost completely. We conclude that VEGF protein and VEGF mRNA expression lev els in primate endometrium depend on the steroidal milieu. Anti-angiog enic effects of mifepristone via suppression of VEGF production might represent a mechanism for its quelling effects on endometrium.