HORMONAL-REGULATION OF ANDROGEN RECEPTOR MESSENGER-RNA 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 pr otection analysis. While a single hybridizable species of AR mRNA of a pproximately 11 kb was found in the anterior pituitary gland (AP) and ventral prostate gland (VP), an additional species of AR mRNA, approxi mately 2 kb smaller, was revealed in neural tissues. Furthermore, in t hese neural tissues, hormonal regulation of the two species of mRNA wa s coordinated; long-term castration increased levels of both forms, wh ile testosterone replacement reduced them. The same pattern of regulat ion was observed for the single 11 kb form in the AP. An RNase protect ion assay was validated and utilized to quantitatively analyze the hor monal regulation of AR mRNA. Castration (4 days) resulted in significa ntly increased AR mRNA in the AP and hypothalamic-preoptic area, but n ot the amygdala, which subsequent administration of dihydrotestosteron e (DHT; 1 day; 2 mg/animal) significantly decreased. In the AP, admini stration of estradiol benzoate (EB) for 1 or 5 days also reversed this effect. However, EB treatment increased the amount of total RNA isola ted per gland. Consequently, when the data are normalized to RNA conte nt per gland, 5 days of EB treatment resulted in a significant increas e in AR mRNA content. These findings suggest that in contrast to the A P and VP, two forms of androgen receptor mRNA exist in the brain. In a ddition, there appears to be tissue and hormone specific regulation of AR mRNA.