Regulation of androgen receptor mRNA expression in hamster facial motoneurons: differential effects of non-aromatizable and aromatizable androgens

Abstract

We have previously shown inherent sex differences in the levels of androgen receptor mRNA (AR mRNA) in hamster facial motor neurons (FMN). FMN of intact females contained approximately 50% less AR mRNA than their male counterparts. Gonadectomy in males down-regulated AR mRNA levels in FMN by approximately 50%, whereas no effects of gonadectomy were observed in females. Sex differences in the regulation of AR mRNA levels by exogenous testosterone propionate (TP) were also observed. In those studies, AR mRNA levels were up-regulated after 1 day of treatment with exogenous TP in FMN of gonadectomized (GDX) males and after 7 days in FMN of intact females, with no effects in GDX females. Since TP is aromatizable to estrogen, and given recent findings of transient expression of estrogen receptors (ER) in rodent FMN, the effects of dihydrotestosterone (DHT), a non-aromatizable form of the steroid, on AR mRNA expression in hamster FMN were examined in the present study. If testosterone (TES) were the active hormone regulating AR mRNA levels in FMN, DHT treatment should render a similar regulatory pattern as TP, but if metabolism of TES to estradiol plays a role in AR mRNA regulation, effects of the two treatments should differ. In situ hybridization and computerized image analysis were used to quantify the regulation of AR mRNA by DHT in individual FMN of hamsters of both sexes. Exogenous DHT was administered to intact and gonadectomized (GDX) male and female hamsters by implantation of one 10-mm Silastic capsule for 1, 2 or 7 days. AR mRNA levels were significantly up-regulated in intact females at all time points of DHT exposure, with no effects in GDX groups. These results differ from previous work using TP, in which a modest up-regulation in AR mRNA levels was observed in FMN of intact females only after 7 days. As with TP, DHT exposure gradually down-regulated AR mRNA levels in FMN of intact males. Thus, DHT only regulated AR mRNA levels in intact animals, with endogenous sources of estrogen available, but not in GDX animals, with endogenous estrogens reduced by gonadectomy. Taken together, these results substantiate our previous findings of sex differences in AR mRNA levels/regulation and suggest a synergism between estrogen and androgen in the regulation of AR mRNA levels in peripheral motor neurons.