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) expression in cultured endothelial cells. To clarify the role of mRNA stabilization 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 of eNOS mRNA. As tumor necrosis factor-alpha. (TNF-alpha) is associated with the progression of atherosclerosis, we examined the effect of 17 beta -estradiol on eNOS mRNA destabilization with TNF-alpha. After 10 hours co-incubation with TNF-alpha, relative intensity of eNOS mRNA decreased to 50% of the intensity at the start time of incubation, however, it remained significantly 1.6 times in the presence of 17 beta -estradiol. This inhibitory effect of 17 beta -estradiol was abolished by the treatment of estrogen receptor antagonist, ICI 182,780. This is the first finding that 17 beta -estradiol stabilizes eNOS mRNA destabilized by TNF-alpha through estrogen receptor mediated mechanism. (C) 2001 Elsevier Science Inc. All rights reserved.