Synthesis and phosphorylation of androgen receptor of the mouse brain cortex and their regulation by sex steroids during aging.

To examine the synthesis and phosphorylation of androgen receptor (AR) and their regulation by sex steroids, adult (24 weeks) and old (65 weeks) male and female mice were gonadectomized and administered with testosterone and estradiol. AR amount, synthesis and phosphorylation were measured in the brain cortex by immunoblotting and immunoprecipitation using antibody raised against rat AR transactivation domain (TAD) which was expressed in E. coli as a fusion protein. We found that the amount of AR was high in adult and declined in old mice of both sexes. Administration of testosterone and estradiol significantly down-regulated the level of AR in old male and adult female. Similarly, the rate of AR synthesis also declined with age. Exogenous treatment of gonadectomized mice with testosterone and estradiol reduced the extent of synthesis significantly in all groups except in old female. No sex-dependent variation was noticed either in the level or synthesis of AR. In contrast, the extent of phosphorylation was higher in old mice of both sexes as compared to their adult counterparts. Testosterone and estradiol supplementation resulted in remarkable increase in AR phosphorylation in all groups. Thus it is evident from our findings that the amount and synthesis of AR decrease but phosphorylation of AR increases in the brain cortex with advancing age of mice and they are regulated by testosterone and estradiol in age- and sex-specific manner.