STEROID CONTROL OF MOTONEURON NUMBER AND CONNECTIVITY

使用一个简单的神经肌肉系统，这个建议的重点是影响 雄激素对正常发育过程中细胞机制的影响 这些神经元在神经元数量、形态和 连通性。 提出的实验研究了两个 性二形核在大鼠脊髓，脊神经核的 球海绵体肌（SNB）和背外侧核（DLN）。 这些核 神经支配会阴部的肌肉，它们的神经核和肌肉都是神经元。 受神经支配的存在于雄性中，但在雌性中减少或不存在。 它有 已经确定，SNB中的性别差异是由一个 雄激素调节的细胞死亡，以及可能的雄激素增强 从DLN迁移到SNB。 由于SNB的发展与 DLN运动神经元数目和传出投射的二型性 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 解决雄激素是否直接或间接促进运动神经元 生存，并将进一步确定雄激素是否单独作用或 与其雌激素代谢物组合以使SNB/DLN雄性化 系统 最后，将在女性中检查SNB和DLN的发育 产前用丙酸双氢睾酮（DHTP）治疗。 这些 女性矛盾地缺乏SNB运动神经元，但保留其会阴 肌肉组织，现在由运动神经元支配， 的DLN。 确定DHTP是否积极抑制了 瑞士央行或只是被动地未能促进其生存将屈服 关于通常控制细胞迁移，死亡， 和规格，以及进一步阐明雄激素的影响， 在这些发展过程中。 更好地理解 性分化的细胞机制为人类的 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.