Darrington R Siobhan, Leigh P Nigel, Gallo Jean-Marc
Department of Neurology, Institute of Psychiatry, King's College London, Box PO38, De Crespigny Park, London, SE5 8AF, UK.
Neurosci Lett. 2003 Oct 16;350(1):37-40. doi: 10.1016/s0304-3940(03)00853-x.
Spinal and bulbar muscular atrophy is a motor neuronopathy caused by a polyglutamine expansion in the androgen receptor (AR). Only males are affected as the development of pathology requires high levels of circulating androgens. Androgens promote aggregation of the AR into characteristic intracellular inclusions. As a potential factor contributing to the protection of female carriers, we assessed the effects of estrogens on AR aggregation in transfected neuronal cells using a filter retardation assay. Pre-treatment of mouse neuroblastoma Neuro2a cells expressing an AR with 51 glutamine residues with 10 microM 17beta- or 17alpha-estradiol prevented induction of AR aggregation by testosterone. Western blot analysis showed that the protective effects of estrogens occurred in the absence of a change in AR processing. We conclude that estrogens protect polyglutamine-expanded AR from aggregation through a non-genomic mechanism possibly involving estrogen binding to the AR.
脊髓延髓肌肉萎缩症是一种由雄激素受体（AR）中多聚谷氨酰胺扩展引起的运动神经元病。只有男性会受影响，因为病理发展需要高水平的循环雄激素。雄激素会促使AR聚集成特征性的细胞内包涵体。作为有助于保护女性携带者的一个潜在因素，我们使用滤膜阻滞试验评估了雌激素对转染神经元细胞中AR聚集的影响。用10微摩尔的17β-或17α-雌二醇预处理表达含有51个谷氨酰胺残基的AR的小鼠神经母细胞瘤Neuro2a细胞，可防止睾酮诱导AR聚集。蛋白质印迹分析表明，雌激素的保护作用在AR加工过程未发生变化的情况下出现。我们得出结论，雌激素通过一种可能涉及雌激素与AR结合的非基因组机制保护多聚谷氨酰胺扩展的AR不发生聚集。
