STEROID HORMONES AND NEURONAL REGENERATION

描述：研究者已经确定了睾酮的作用 丙酸（TP）在促进挤压面部神经元再生中的作用 成年仓鼠的神经据认为，睾丸激素介导其 通过雄激素受体（AR）的作用，在男性中更普遍 比女性的要多，并且存在于这个特殊的神经元的表面， 亚型以前，一个工作模型的机制，类固醇 已经开发了增强的周围神经再生。主要 该项目的目标是测试该模型的特定方面， 特别关注再生反应的初始损伤阶段 以及雄激素受体在这些早期现象中的作用。的 目的是检验以下四个假设。首先，它表明TP 与面神经损伤同时给药改变早期应激 受伤的FMN。两个系列的实验，利用北方 与热休克蛋白70结合的印迹和免疫印迹方法 cDNA探针和抗体将用于确定TP对细胞凋亡的影响。 损伤FMN的应激反应。第二，TP对面部的影响 在FMN损伤的最初阶段发生神经再生 尽管所有以前的研究都使用TP给药， 很长的时间。为了了解TP是否可以在早期起作用，TP暴露将 限制在面神经损伤后6-2小时的时间段和2 将进行一系列分析。放射性同位素标记程序将 用于确定有限的Tp暴露对面部疾病发生率的影响。 神经再生和原位杂交研究与细胞骨架 将进行探测以确定有限TP暴露对 整个恢复期的细胞骨架反应模式。三是 TP促进面神经再生的性别差异 是AR介导的。在3个系列的实验中，雌性动物将在 面神经损伤，以上调AR mRNA水平， 男性，以及TP对面神经再生的影响，以及 将测定rRNA/细胞骨架基因表达。四、雌二醇 (E)通过AR起作用以增强种族神经再生。已经表明 从面部神经损伤时开始给予E，导致雄激素- 比如加速再生率。两个系列的实验将是 完了在抗雄激素的存在下高剂量E的作用， 氟替卡松，高剂量与低剂量的E对再生率的影响将 下定决心。还将进行AR结合试验，以确定E是否结合 到面神经核的AR

DESCRIPTION: The investigator has identified a role for testosterone propionate (TP) in enhancing neuronal regeneration of the crushed facial nerve in adult hamsters. It is thought that testosterone mediates its actions through androgen receptors (AR) that are more prevalent in males than in females and are present at the surface of this particular neuronal subtype. Previously, a working model of the mechanism by which steroids augment peripheral nerve regeneration has been developed. The main objective of this project is to test specific aspects of this model, with particular focus on the initial injury phases of the regenerative response and on the role of the androgen receptor in these early phenomena. The aims are to test the following 4 hypotheses. First, it was shown that TP administration coincident with facial nerve injury alters early stress responses of injured FMN. Two series of experiments, utilizing northern blot and immunoblot procedures in conjunction with heat shock protein 70 cDNA probes and antibodies will be used to determine the effect of TP on the stress response of injured FMN. Second, the effects of TP on facial nerve regeneration occur during the initial stages of the FMN injury response although all previous studies have used TP administration for lengthy time periods. To learn if TP can work early on, TP exposure will be limited to time periods of 6-2 hours after facial nerve injury and 2 series of analyses will be done. Radioisotopic labeling procedures will be used to determine the effects of limited Tp exposure on the rate of facial nerve regeneration, and in situ hybridization studies with cytoskeletal probes will be done to determine the effects of limited TP exposure on cytoskeletal response patterns throughout the recovery period. Third, the gender differences in the augmentation of facial nerve regeneration by TP are AR mediated. In 3 series of experiments, females will receive TP prior to facial nerve injury, in order to up-regulate levels of AR mRNA to those of males, and the effects of TP on facial nerve regeneration, and rRNA/cytoskeletal gene expression will be determined. Fourth, estradiol (E) acts via AR to augment racial nerve regeneration. It has been shown that E given from the time of facial nerve injury, results in an androgen- like acceleration of regeneration rates. Two series of experiments will be done. The effects of high doses of E in the presence of the anti-androgen, flutamide, and high versus low doses of E on the rate of regeneration will be determined. AR binding assays will also be done to determine if E binds to AR in the facial nucleus.