Sex differences in androgen receptor mRNA levels and regulation in hamster facial motoneurons

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.