Tanzer L, Jones K J
Department of Cell Biology, Neurobiology and Anatomy, Loyola University Chicago, Illinois, USA.
Exp Neurol. 1997 Jul;146(1):258-64. doi: 10.1006/exnr.1997.6529.
We have demonstrated, in a series of experiments, the therapeutic potential of androgens in facial motoneuron regeneration in the adult hamster. Initial work utilized testosterone propionate (TP) as the form of androgen given to adult hamster at the time of facial nerve crush axotomy at its exit from the stylomastoid foramen. TP is capable of being enzymatically converted to estrogen. Thus, the effects of TP on the regenerative properties of facial motoneurons could be due to androgens, estrogens, or both. Recent studies of androgen receptor (AR) mRNA levels suggest that androgens and estrogens work synergistically to regulate AR expression in these motoneurons. In this study, we examined the ability of dihydrotestosterone propionate (DHTP), a nonaromatizable androgen which cannot be converted to estrogen, and estradiol (E2) to alter facial nerve regeneration, using fast axonal transport of radioactively labeled proteins to assess facial nerve regeneration. Adult gonadectomized male hamsters were subjected to right facial nerve crush axotomy, with the left side serving as control, and divided into three groups. One-third of the animals received 1 subcutaneous implant of DHTP, one-third received 1 subcutaneous implant of E2, and the remaining third was sham implanted. Postoperative survival times were 4 and 7 days. As expected, DHTP treatment resulted in an approximately 40% increase in the rate of regeneration, with an associated prolongation in the delay time before sprouting occurred. These effects were slightly greater than previously observed with TP, as might be predicted given the more potent physiological effects observed with DHTP compared to TP. Surprisingly, E2 treatment also resulted in an increase in the rate of regeneration (30%), with minimal effects on the delay time before sprout formation occurred. The results argue for a synergistic role for androgens and estrogens in augmenting peripheral nerve regeneration in the model system used in this study.
在一系列实验中，我们已经证明了雄激素在成年仓鼠面部运动神经元再生方面的治疗潜力。最初的研究使用丙酸睾酮（TP）作为雄激素的形式，在成年仓鼠面神经从茎乳孔穿出时进行挤压性轴突切断术后给予。TP能够被酶转化为雌激素。因此，TP对面部运动神经元再生特性的影响可能是由于雄激素、雌激素或两者共同作用。最近关于雄激素受体（AR）mRNA水平的研究表明，雄激素和雌激素协同作用来调节这些运动神经元中的AR表达。在本研究中，我们使用放射性标记蛋白质的快速轴突运输来评估面神经再生，研究了丙酸双氢睾酮（DHTP，一种不能转化为雌激素的非芳香化雄激素）和雌二醇（E2）改变面神经再生的能力。成年去势雄性仓鼠接受右侧面神经挤压性轴突切断术，左侧作为对照，并分为三组。三分之一的动物接受1次皮下植入DHTP，三分之一接受1次皮下植入E2，其余三分之一进行假植入。术后存活时间为4天和7天。正如预期的那样，DHTP治疗使再生速率提高了约40%，同时发芽前的延迟时间延长。这些效果比之前用TP观察到的略大，这正如根据与TP相比DHTP观察到的更强生理效应所预测的那样。令人惊讶的是，E2治疗也导致再生速率增加（30%），对发芽形成前的延迟时间影响最小。结果表明，在本研究使用的模型系统中，雄激素和雌激素在增强周围神经再生方面具有协同作用。
