Sex steroids reduce DNaseI accessibility of androgen receptor promoter in adult male mice brain.

We have previously reported that androgen receptor (AR) expression is inversely correlated to its promoter methylation and is regulated by sex steroids. As chromatin structure plays an important role in transcriptional regulation, the effect of sex steroids on DNaseI accessibility of chromatin of AR promoter was examined in the brain cortex of adult and old mice of both sexes. Nuclei were digested with different concentrations of DNaseI and the extracted DNA was further cleaved by PstI and analyzed by Southern hybridization with DIG-labeled 695-bp AR promoter. With 50 U DNaseI, the intensity of PstI-specific 1.45-kb band was lower in intact female as compared to male groups, suggesting increased nuclease accessibility in female than male. Although gonadectomy increased DNaseI accessibility remarkably in male and female of both ages, testosterone decreased the accessibility in adult but increased in old male. Estradiol, on the other hand, decreased DNaseI accessibility in both adult male and old female but increased in old male and adult female. Thus, these findings suggest that the chromatin conformation of AR promoter varies with age and sex and its accessibility to DNaseI is reduced by testosterone and estradiol in the brain cortex of adult male mice.