Brooks B P, Merry D E, Paulson H L, Lieberman A P, Kolson D L, Fischbeck K H
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia 19104-6140, USA.
J Neurochem. 1998 Mar;70(3):1054-60. doi: 10.1046/j.1471-4159.1998.70031054.x.
Androgens are known to alter the morphology, survival, and axonal regeneration of lower motor neurons in vivo. To understand better the molecular mechanisms of androgen action in neurons, we created a model system by stably expressing the human androgen receptor (AR) in motor neuron hybrid cells. Motor neuron hybrid cells express markers consistent with anterior horn cells and can be differentiated into a neuronal phenotype. When differentiated in the presence of androgen, AR-expressing cells, but not control cells, exhibit a dose-dependent change in morphology: androgen-treated cells develop larger cell bodies and broader neuritic processes while continuing to express neuronal markers. In addition, androgen promotes the survival of AR-expressing cells, but not control cells, under low-serum conditions. Our results demonstrate a direct trophic effect of androgens on lower motor neurons, mediated through the AR expressed in this population of neurons.
已知雄激素可在体内改变下运动神经元的形态、存活及轴突再生。为了更好地理解雄激素在神经元中的作用分子机制,我们通过在运动神经元杂交细胞中稳定表达人雄激素受体(AR)创建了一个模型系统。运动神经元杂交细胞表达与前角细胞一致的标志物,并且可以分化为神经元表型。当在雄激素存在的情况下进行分化时,表达AR的细胞而非对照细胞呈现出剂量依赖性的形态变化:经雄激素处理的细胞形成更大的细胞体和更宽的神经突,同时继续表达神经元标志物。此外,在低血清条件下,雄激素可促进表达AR的细胞而非对照细胞的存活。我们的结果证明了雄激素对下运动神经元具有直接的营养作用,这是通过该群体神经元中表达的AR介导的。