STEROID CONTROL OF MOTONEURON NUMBER AND CONNECTIVITY

使用一个简单的神经肌肉系统，这项建议侧重于影响 雄激素对正常发育过程中细胞机制的影响 这会导致神经元数量、形态和性别的差异 连通性。提出的实验考察了两个方面的发展 大鼠脊髓内的性二形核、脊髓核 球海绵体(SNB)和背外侧核(DLN)。这些核团 支配会的肌肉，它们的核和肌肉 神经支配在雄性中存在，但在雌性中减少或不存在。它有 已经确定瑞士央行的性别差异是由 雄激素调节的细胞死亡以及可能的雄激素增强 瑞士央行从DLN迁移的。因为瑞士央行的发展与 DLN，DLN的二态运动神经元数目和传出投射 将检查开发，以测试雄激素对促进 轴突生长和细胞存活。其次，几个实验将 探讨雄激素是直接还是间接促进运动神经元 生存，并将进一步定义雄激素是单独起作用还是在 与其雌激素代谢物结合使SNB/DLN男性化 系统。最后，将检查女性SNB和DLN的发育情况。 产前使用丙酸双氢睾丸酮(DHTP)治疗。这些 自相矛盾的是，女性缺少SNB运动神经元，但保留了会阴 肌肉系统，现在由异常分布在 DLN。确定DHTP是否积极抑制糖尿病的发生 瑞士央行或仅仅是被动地未能促进其生存将会屈服 关于通常控制细胞迁移、死亡、 以及进一步阐明雄激素的影响 关于开发过程中的这些过程。更好地理解 性分化的细胞机制为 治疗/预防人类性分化异常。

Using a simple neuromuscular system, this proposal focuses on the influence of androgens on the cellular mechanisms operating during normal development which produce sex differences in neuron number, morphology, and connectivity. The experiments proposed examine the development of two sexually dimorphic nuclei in the rat spinal cord, the spinal nucleus of the bulbocavernosus (SNB) and the dorsolateral nucleus (DLN). These nuclei innervate muscles of the perineum, and both the nuclei and the muscles they innervate are present in males but reduced or absent in females. It has been established that the sex difference in the SNB is produced by an androgen-regulated cell death, as well as a possible androgen enhancement of SNB migration from the DLN. Because SNB development is related to the DLN, how the DLN's dimorphic motoneuron number and efferent projections develop will be examined to test the influence of androgens on promoting axon outgrowth and cell survival. Secondly, several experiments will address whether androgens act directly or indirectly to promote motoneuron survival, and will further define whether androgens act alone or in combination with their estrogenic metabolites to masculinize the SNB/DLN system. Finally, SNB and DLN development will be examined in females treated prenatally with dihydrotestosterone propionate (DHTP). These females paradoxically lack SNB motoneurons but retain their perineal musculature, which is now innervated by motoneurons anomalously located in the DLN. Determining whether DHTP actively inhibits the development of the SNB or merely passively fails to promote its survival will yield information on the factors which normally control cell migration, death, and specification, as well as further clarifying the influence of androgens on these processes during development. A better understanding of the cellular mechanisms of sexual differentiation holds great promise for the treatment/prevention of abnormalities of sexual differentiation in humans.