Hormonal regulation of androgen receptor mRNA in the brain and anterior pituitary gland of the male rat

To determine possible cellular mechanisms governing androgen action in the brain, we examined the hormonal regulation of androgen receptor (AR) mRNA in neural tissues by Northern blot hybridization and RNase protection analysis. While a single hybridizable species of AR mRNA of approximately 11 kb was found in the anterior pituitary gland (AP) and ventral prostate gland (VP), an additional species of AR mRNA, approximately 2 kb smaller, was revealed in neural tissues. Furthermore, in these neural tissues, hormonal regulation of the two species of mRNA was coordinated; long-term castration increased levels of both forms, while testosterone replacement reduced them. The same pattern of regulation was observed for the single 11 kb form in the AP. An RNase protection assay was validated and utilized to quantitatively analyze the hormonal regulation of AR mRNA. Castration (4 days) resulted in significantly increased AR mRNA in the AP and hypothalamic-preoptic area, but not the amygdala, which subsequent administration of dihydrotestosterone (DHT; 1 day; 2 mg/animal) significantly decreased. In the AP, administration of estradiol benzoate (EB) for 1 or 5 days also reversed this effect. However, EB treatment increased the amount of total RNA isolated per gland. Consequently, when the data are normalized to RNA content per gland, 5 days of EB treatment resulted in a significant increase in AR mRNA content. These findings suggest that in contrast to the AP and VP, two forms of androgen receptor mRNA exist in the brain. In addition, there appears to be tissue and hormone specific regulation of AR mRNA.