Transcription of estrogen receptor α and β in mouse cerebral cortex: Effect of age, sex, 17β-estradiol and testosterone

Estrogen actions are mainly mediated by estrogen receptor (ER)α and ERβ which in turn are regulated by several factors including age, sex and gonadal steroid hormones 17β-estradiol and testosterone. In the present study, we have used nuclear run-off assay to examine the effect of these factors on the rate of transcription of ERα and ERβ of mouse cerebral cortex. The run-off assay result was further corroborated with the measurement of steady state level of ERα and ERβ mRNA by semiquantitative RT-PCR method. Our results reveal that ERα transcription rate decreases in old mice of both sexes, whereas ERβ transcription rate decreases only in old females when compared to their adult counterparts. 17β-Estradiol supplementation reduces the transcription rate of ERα and ERβ in all groups except in adult male while testosterone treatment down regulates the transcription rate of ERα and ERβ in all groups. The semiquantitative RT-PCR analysis reveals that the level of ERα mRNA decreases in old male but shows no effect in old female as compared to adult counterpart. In contrast, ERβ transcript level decreases in old mice of both sexes. Furthermore, ERα mRNA level is higher in adult female than in adult male but no sex-dependent difference is seen in ERβ mRNA level. Supplementation of 17β-estradiol shows no significant alteration but testosterone reduces the ERα level in male mice, while 17β-estradiol and testosterone down regulate the ERα level in female mice of both ages. In case of ERβ, 17β-estradiol decreases the transcript level in all groups except adult male while testosterone treatment results in the down regulation of transcript level in all groups. Thus these findings suggest differential effects of age, sex, 17β-estradiol and testosterone supplementation on the transcription of mouse ER genes which may account for differences in the protein levels of ERα and ERβ and their functions in the brain.