Estrogen prevents destabilization of endothelial nitric oxide synthase mRNA induced by tumor necrosis factor ox through estrogen receptor mediated system

17 beta -estradiol up-regulates endothelial nitric oxide synthase (eNOS) ex pression in cultured endothelial cells. To clarify the role of mRNA stabili zation in upregulation of eNOS expression, endothelial cells were incubated with actinomycin D as transcriptional inhibitor. Up to 10 hours incubation with 17 beta -estradiol alone did not affect significantly the stability o f eNOS mRNA. As tumor necrosis factor-alpha. (TNF-alpha) is associated with the progression of atherosclerosis, we examined the effect of 17 beta -est radiol on eNOS mRNA destabilization with TNF-alpha. After 10 hours co-incub ation with TNF-alpha, relative intensity of eNOS mRNA decreased to 50% of t he intensity at the start time of incubation, however, it remained signific antly 1.6 times in the presence of 17 beta -estradiol. This inhibitory effe ct of 17 beta -estradiol was abolished by the treatment of estrogen recepto r antagonist, ICI 182,780. This is the first finding that 17 beta -estradio l stabilizes eNOS mRNA destabilized by TNF-alpha through estrogen receptor mediated mechanism. (C) 2001 Elsevier Science Inc. All rights reserved.