DISRUPTION OF ESTROGEN-RECEPTOR GENE PREVENTS 17-BETA ESTRADIOL-INDUCED ANGIOGENESIS IN TRANSGENIC MICE

Estrogen is known to modulate angiogenesis, both under physiological a nd pathological conditions, and has been demonstrated to augment angio genesis induced by bFGF in a mouse model. We have modified this mouse model and measured the apparent plasma volume in Matrigel plugs contai ning basic fibroblast growth factor (bFGF) in wild type and estrogen r eceptor knockout, ovariectomized mice in the presence and absence of e xogenous 17 beta estradiol. The apparent plasma volume was determined by measuring the fluorescence of the excised plug 10 min. after inject ion of fluoroscein labeled dextran 150. In wild type mice exogenous 17 beta estradiol increased the apparent plasma volume of the Matrigel p lug and the uterine weight significantly. In the estrogen receptor kno ckout mice exogenous 17 beta estradiol caused a small, but significant increase in uterine weight but was without effect on the apparent pla sma volume of the Matrigel plug. It is concluded that functional estro gen receptors are essential for the augmentation of bFGF-induced angio genesis by exogenous 17 beta estradiol in female mice.