Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana 47405, USA.
Endocrinology. 2011 Feb;152(2):639-50. doi: 10.1210/en.2010-1197. Epub 2010 Dec 8.
The dendritic arbors of spinal motoneurons are dynamically regulated by a variety of factors, and several lines of evidence indicate that trophic interactions with the target musculature are of central importance. In highly androgen-sensitive motoneuron populations, androgens are thought to regulate motoneuron dendrites through their action at the receptor-enriched target musculature. Using rats transgenically modified to overexpress androgen receptor (AR) in skeletal muscle, we directly tested the hypothesis that the enhanced expression of AR in the target musculature can underlie the androgenic regulation of motoneuron dendritic morphology. The morphology of motoneurons innervating the quadriceps muscle was examined in wild-type (WT) rats as well as in rats that had been transgenically modified to overexpress ARs in their skeletal musculature. Motoneurons innervating the vastus lateralis muscle of the quadriceps in gonadally intact male rats, and castrated males with or without androgen replacement, were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. In WT rats, quadriceps motoneuron dendrites were insensitive to hormonal manipulation. In contrast, quadriceps motoneuron dendrites in gonadally intact transgenic males were larger than those of WT males. Furthermore, overexpression of ARs in the quadriceps muscle resulted in androgen sensitivity in dendrites, with substantial reductions in dendritic length occurring after castration; this reduction was prevented with testosterone replacement. Thus, it appears that the androgen sensitivity of motoneuron dendrites is conferred indirectly via the enrichment of ARs in the musculature.
脊髓运动神经元的树突分支由多种因素动态调节，有几条证据表明与靶肌肉的营养相互作用至关重要。在高度雄激素敏感的运动神经元群体中，雄激素被认为通过其在富含受体的靶肌肉中的作用来调节运动神经元树突。我们使用转基因大鼠过度表达骨骼肌中的雄激素受体 (AR)，直接检验了靶肌肉中 AR 表达增强可以为运动神经元树突形态的雄激素调节提供基础的假设。在野生型 (WT) 大鼠以及骨骼肌中过度表达 AR 的转基因大鼠中检查了支配股四头肌的运动神经元的形态。用霍乱毒素结合辣根过氧化物酶标记支配股四头肌股外侧肌的神经支配，重建三维树突分支。在 WT 大鼠中，股四头肌运动神经元树突对激素处理不敏感。相比之下，在性腺完整的转基因雄性大鼠以及去势雄性大鼠（无论是否用雄激素替代）中，股四头肌运动神经元树突较大。此外，在股四头肌中过度表达 AR 会导致树突对雄激素敏感，去势后树突长度显著减少；这种减少可以用睾酮替代来预防。因此，运动神经元树突的雄激素敏感性似乎是通过肌肉中 AR 的富集间接赋予的。
