Drengler S M, Handa R J, Jones K J
Department of Cell Biology, Loyola University Chicago, Maywood, IL 60153, USA.
Brain Res Mol Brain Res. 1996 Jan;35(1-2):131-8. doi: 10.1016/0169-328x(95)00197-z.
We have previously shown that testosterone propionate augments hamster facial nerve regeneration to a greater extent in males than females. Further, sex differences in facial nerve regeneration have been observed. From those studies, we hypothesized that sex differences in nerve regeneration could be due to inherent differences in androgen receptor (AR) mRNA content within facial motor neurons (FMN) of male and female hamsters. In the present study, that hypothesis was tested using in situ hybridization, and computerized image analysis to quantify levels and regulation of AR mRNA in individual FMN of hamsters of both sexes. Intact and gonadectomized (gdx) male and female hamsters were used in the initial experiments in the study. In subsequent experiments, exogenous testosterone propionate (TP) was administered to the aforementioned groups of animals by subcutaneous implantation of one 10-mm Silastic capsule for 1, 2 or 7 days. FMN of intact females contained approximately 50% less AR mRNA than their male counterparts. Gonadectomy in males downregulated AR mRNA levels by approximately 50%, whereas no effects of gonadectomy were observed in females. Thus, in all paradigms where TP levels were low relative to the intact males, AR mRNA levels were approximately half of those in the intact male FMN. TP administration induced AR mRNA levels in gdx males within 1 day. Significant effects of TP were not detected in gdx females, and only after 7 days in the intact females. To our knowledge, the results of this study are the first quantitative demonstration of sex differences in steroid receptor mRNA content in a given neuronal population and substantiate the idea that sex differences in the effects of androgens on peripheral nerve regeneration are based on intrinsic sex differences in the levels and regulation of receptor mRNA in motor neurons.
我们之前已经表明，丙酸睾酮对仓鼠面神经再生的促进作用在雄性中比雌性更为显著。此外，人们还观察到面神经再生存在性别差异。基于这些研究，我们推测神经再生的性别差异可能是由于雄性和雌性仓鼠面部运动神经元（FMN）中雄激素受体（AR）mRNA含量的固有差异所致。在本研究中，我们使用原位杂交和计算机图像分析来量化两性仓鼠单个FMN中AR mRNA的水平和调控，从而验证这一假设。在该研究的初始实验中，使用了完整的和去势的雄性和雌性仓鼠。在后续实验中，通过皮下植入一个10毫米的硅橡胶胶囊，分别给上述几组动物注射外源性丙酸睾酮（TP）1天、2天或7天。完整雌性的FMN中AR mRNA含量比雄性对应物少约50%。雄性去势使AR mRNA水平下调约50%，而雌性去势未观察到影响。因此，在所有相对于完整雄性TP水平较低的实验范式中，AR mRNA水平约为完整雄性FMN中的一半。给去势雄性注射TP后1天内可诱导AR mRNA水平升高。在去势雌性中未检测到TP的显著影响，在完整雌性中仅在7天后才检测到。据我们所知，本研究结果首次定量证明了特定神经元群体中类固醇受体mRNA含量存在性别差异，并证实了雄激素对外周神经再生影响的性别差异是基于运动神经元中受体mRNA水平和调控的内在性别差异这一观点。
