Niino Masaaki, Hirotani Makoto, Fukazawa Toshiyuki, Kikuchi Seiji, Sasaki Hidenao
Department of Neurology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kitaku, Sapporo, Japan.
Cent Nerv Syst Agents Med Chem. 2009 Jun;9(2):87-94. doi: 10.2174/187152409788452054.
The disease activity of multiple sclerosis (MS) is known to be ameliorated during pregnancy, and pregnancy is also found to be protective in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Estrogen levels increase during pregnancy and basic researches have shown that estrogens have immunomodulatory effects on immune cells. The importance of estrogen in pathogenic autoimmune diseases has also been demonstrated in EAE by altering hormone levels. Mice treated with estrogen experienced significantly decreased EAE severity and delayed onset of disease as a result of neuroprotective and anti-inflammatory effects. Brain atrophy has been detected at the early stages of MS by using MRI; thus, as a neuroprotective agent, estrogen might be effective against brain atrophy. Estrogen's effects are primarily mediated by the nuclear estrogen receptor (ER), and recent studies have shown the presence of nuclear ERs on the cells involved in the immune response. There have been some reports on genetic polymorphisms of ERs in MS. In this review paper, we discuss increasing evidence that points to a link between estrogen and MS. We also analyze the therapeutic potential of estrogens in MS and review current genetic studies on ER.
已知多发性硬化症（MS）的疾病活动在孕期会有所改善，并且在实验性自身免疫性脑脊髓炎（EAE，一种MS的动物模型）中也发现怀孕具有保护作用。孕期雌激素水平会升高，基础研究表明雌激素对免疫细胞具有免疫调节作用。通过改变激素水平，雌激素在致病性自身免疫性疾病EAE中的重要性也得到了证实。接受雌激素治疗的小鼠由于神经保护和抗炎作用，EAE严重程度显著降低且疾病发病延迟。通过使用MRI在MS早期已检测到脑萎缩；因此，作为一种神经保护剂，雌激素可能对脑萎缩有效。雌激素的作用主要由核雌激素受体（ER）介导，最近的研究表明在参与免疫反应的细胞上存在核ER。关于MS中ER的基因多态性已有一些报道。在这篇综述论文中，我们讨论了越来越多的证据表明雌激素与MS之间存在联系。我们还分析了雌激素在MS中的治疗潜力，并综述了目前关于ER的基因研究。
