Estradiol (e2) regulates vascular endothelial growth factor (vegf) itlrna in the uterus

VEGF is a potent angiogenic factor that affects normal and abnormal growth by inducing new blood vessels, and also functions as a vascular permeability factor. Since E2 increases both vascular permeability and angiogenesis in the female reproductive tract, we have used the rat uterus to study estrogen regulation of VEGF transcription by northern blot analysis. In ovariectomized rats E2 causes a 10-20 fold increase in VEGF in 1-3 hours. Induction is dose dependent with a maximum response produced by a dose of 0.4 Mg/kg E2. Induction is specific for estrogens, inhibited by actinomycin D, but unaffected by puromycin; suggesting this is a transcriptional effect mediated by the classical estrogen receptor system. These results indicate that VEGF expression is increased during E2 induced growth of the reproductive tract, and raise the possibility that estrogen effects on the cardiovascular system may also involve the regulation of this factor.