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

Estrogen actions are mainly mediated by estrogen receptor (ER)alpha and ER beta which in turn are regulated by several factors including age, sex and gonadal steroid hormones 17 beta-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 ER alpha. and ER beta of mouse cerebral cortex. The run-off assay result was further corroborated with the measurement of steady state level of ERa. and ER beta mRNA by serniquantitative RT-PCR method. Our results reveal that ERU transcription rate decreases in old mice of both sexes, whereas ER beta transcription rate decreases only in old females when compared to their adult counterparts. 17 beta-Estradiol supplementation reduces the transcription rate of ER alpha and ER beta in all groups except in adult male while testosterone treatment down regulates the transcription rate of ER alpha and ER beta in all groups. The serniquantitative RT-PCR analysis reveals that the level of ER alpha mRNA decreases in old male but shows no effect in old female as compared to adult counterpart. In contrast, ER beta transcript level decreases in old mice of both sexes. Furthermore, ER alpha mRNA level is higher in adult female than in adult male but no sex-dependent difference is seen in ER beta mRNA level. Supplementation of 17 beta-estradiol shows no significant alteration but testosterone reduces the ERa level in male mice, while 17 beta-estradiol and testosterone down regulate the ER alpha level in female mice of both ages. In case of ERP, 17 beta-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, 17 beta-estradiol and testosterone supplementation on the transcription of mouse ER genes which may account for differences in the protein levels of ER alpha and ER beta and their functions in the brain. (c) 2006 Elsevier Ltd. All rights reserved.