Hayashi T, Yamada K, Esaki T, Muto E, Chaudhuri G, Iguchi A
Department of Geriatrics, Nagoya University School of Medicine, Japan.
J Cardiovasc Pharmacol. 1998 Feb;31(2):292-8. doi: 10.1097/00005344-199802000-00016.
We investigated the effect of estrogen on inducible nitric oxide synthase (iNOS), which is not well understood, in contrast to the known effect of estrogen on endothelial nitric oxide synthase (eNOS). When J774 cells, a murine macrophage cell line, were incubated with interferon-gamma and lipopolysaccharide, iNOS was induced, and a large amount of NO was released. Pre- or coincubation with 17beta-estradiol inhibited this induction of iNOS protein and NO release; however, 17beta-estradiol did not have a direct effect on enzyme activity of iNOS. The analog, 17alpha-estradiol, did not have such an effect. Tamoxifen, an antiestrogen, and ICI182780, an estrogen-receptor antagonist, inhibited the influence of 17beta-estradiol on iNOS. Thus 17beta-estradiol inhibited the induction of iNOS by a classic receptor-mediated pathway. The inhibition of the NO release from iNOS by 17beta-estradiol is in contrast to the reported augmentation of continuous NO release from eNOS. These harmonious effects of estrogen on iNOS and eNOS may have some role in the antiatherosclerotic effects of 17beta-estradiol.
我们研究了雌激素对诱导型一氧化氮合酶（iNOS）的影响，与雌激素对内皮型一氧化氮合酶（eNOS）的已知作用相比，雌激素对iNOS的影响尚不明确。当将小鼠巨噬细胞系J774细胞与γ干扰素和脂多糖一起孵育时，iNOS被诱导，并且释放出大量的一氧化氮（NO）。预先或同时与17β-雌二醇孵育可抑制iNOS蛋白的这种诱导以及NO的释放；然而，17β-雌二醇对iNOS的酶活性没有直接影响。其类似物17α-雌二醇没有这种作用。抗雌激素药物他莫昔芬和雌激素受体拮抗剂ICI182780抑制了17β-雌二醇对iNOS的影响。因此，17β-雌二醇通过经典的受体介导途径抑制iNOS的诱导。17β-雌二醇对iNOS释放NO的抑制作用与报道的雌激素增强eNOS持续释放NO的作用相反。雌激素对iNOS和eNOS的这些协调作用可能在17β-雌二醇的抗动脉粥样硬化作用中发挥一定作用。
