ESTRADIOL ATTENUATES DIRECTED MIGRATION OF VASCULAR SMOOTH-MUSCLE CELLS IN-VITRO

Although the cardiovascular benefits of the hormone estrogen are at le ast, in part, mediated by its antiproliferative effect on vascular smo oth muscle, its action on the migration of these cells is unknown. To explore this relationship, female rat aortic smooth muscle cells were grown in hormone-free medium, and the effect of various concentrations of beta-estradiol on directed cellular migration was measured in vitr o using a microwell Boyden chamber apparatus. Migration of smooth musc le cells to the known chemoattractants platelet-derived growth factor, insulin-like growth factor-1, and fibronectin (all at peak doses for migratory activity) was attenuated by beta-estradiol (0.5 to 10 ng/ml) in a concentration-dependent manner relative to control cells treated with vehicle (0.01% ethanol). This response was insensitive to pretre atment with indomethacin and was stereospecific (17 alpha-estradiol la cked response), Like beta-estradiol, the synthetic estrogen diethylsti lbestrol attenuated directed smooth muscle cell migration whereas the male hormone testosterone was ineffective. Additional studies showed t hat beta-estradiol-mediated suppression of migration was inhibited by the anti-estrogen ICI 164,384 and tbe gene transcription inhibitor act inomycin D. These are the first results demonstrating a reduction in d irected smooth muscle cell migration by beta-estradiol, The mechanism of this estrogen-mediated response appears to involve conventional est rogen receptors.