Department of Psychological and Brain Sciences and Program in Neuroscience, Indiana University, Bloomington, Indiana, 47405.
Dev Neurobiol. 2013 Dec;73(12):921-35. doi: 10.1002/dneu.22118. Epub 2013 Oct 7.
The spinal cord of rats contains the sexually dimorphic motoneurons of the spinal nucleus of the bulbocavernosus (SNB). In males, SNB dendrites fail to grow after castration, but androgen or estrogen treatment supports dendritic growth in castrated males. Estrogenic support of SNB dendrite growth is mediated by estrogen receptors (ER) in the target muscle. ERα expression in cells lacking a basal lamina (referred to as "extra-muscle fiber cells") of the SNB target musculature coincides with the period of estrogen-dependent SNB dendrite growth. In the SNB target muscle, extra-muscle fiber ERα expression declines with age and is typically absent after postnatal (P) day 21 (P21). Given that estradiol downregulates ERα in skeletal muscle, we tested the hypothesis that depleting gonadal hormones would prevent the postnatal decline in ERα expression in the SNB target musculature. We castrated male rats at P7 and assessed ERα immunolabeling at P21; ERα expression was significantly greater in castrated males compared with normal animals. Because ERα expression in SNB target muscles mediates estrogen-dependent SNB dendrogenesis, we further hypothesized that the castration-induced increase in muscle ERα would heighten the estrogen sensitivity of SNB dendrites. Male rats were castrated at P7 and treated with estradiol from P21 to P28; estradiol treatment in castrates resulted in dendritic hypertrophy in SNB motoneurons compared with normal males. We conclude that early castration results in an increase in ERα expression in the SNB target muscle, and this upregulation of ERα supports estrogen sensitivity of SNB dendrites, allowing for hypermasculinization of SNB dendritic arbors.
大鼠脊髓包含球海绵体神经核（SNB）的性别二态性运动神经元。在雄性中，去势后 SNB 树突停止生长，但雄激素或雌激素处理支持去势雄性中的树突生长。雌激素对 SNB 树突生长的支持是通过 SNB 靶肌肉中的雌激素受体（ER）介导的。缺乏 SNB 靶肌肉基底膜（称为“SNB 靶肌肉中的额外肌纤维细胞”）的细胞中的 ERα 表达与雌激素依赖性 SNB 树突生长时期一致。在 SNB 靶肌肉中，额外肌纤维 ERα 表达随年龄下降，并且通常在出生后（P）第 21 天（P21）后消失。鉴于雌二醇下调骨骼肌中的 ERα，我们检验了假设，即耗竭性腺激素会阻止 SNB 靶肌肉中 ERα 表达的出生后下降。我们在 P7 时对雄性大鼠进行去势，并在 P21 时评估 ERα 免疫标记；与正常动物相比，去势雄性中的 ERα 表达明显更高。由于 SNB 靶肌肉中的 ERα 表达介导雌激素依赖性 SNB 树突发生，我们进一步假设，去势诱导的肌肉 ERα 增加会提高 SNB 树突对雌激素的敏感性。雄性大鼠在 P7 时去势，并在 P21 至 P28 时用雌二醇处理；与正常雄性相比，去势大鼠中的雌二醇处理导致 SNB 运动神经元中的树突肥大。我们得出结论，早期去势导致 SNB 靶肌肉中 ERα 表达增加，这种 ERα 的上调支持 SNB 树突对雌激素的敏感性，从而允许 SNB 树突分支过度男性化。
