Aging and Loss of Circulating 17beta-Estradiol Alters the Alternative Splicing of ERbeta in the Female Rat Brain Journal Article

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Authors: Shults, C. L.; Pinceti, E.; Rao, Y. S.; Pak, T. R.
Article Title: Aging and Loss of Circulating 17beta-Estradiol Alters the Alternative Splicing of ERbeta in the Female Rat Brain
Abstract: Loss of circulating 17beta-estradiol (E2) that occurs during menopause can have detrimental effects on cognitive function. The efficacy of hormone replacement therapy declines as women become farther removed from the menopausal transition, yet the molecular mechanisms underlying this age-related switch in E2 efficacy are unknown. We hypothesized that aging and varying lengths of E2 deprivation alters the ratio of alternatively spliced estrogen receptor (ER)beta isoforms in the brain of female rats. Further, we tested whether changes in global transcriptional activity and splicing kinetics regulate the alternative splicing of ERbeta. Our results revealed brain region-specific changes in ERbeta alternative splicing in both aging and E2-deprivation paradigms and showed that ERbeta could mediate E2-induced alternative splicing. Global transcriptional activity, as measured by phosphorylated RNA polymerase II, was also regulated by age and E2 in specific brain regions. Finally, we show that inhibition of topoisomerase I resulted in increased ERbeta2 splice variant expression.
Journal Title: Endocrinology
Volume: 156
Issue: 11
ISSN: 1945-7170; 0013-7227
Publisher: Unknown  
Journal Place: United States
Date Published: 2015
Start Page: 4187
End Page: 4199
Language: eng
DOI/URL:

10.1210/en.2015-1514
Notes: LR: 20151021; JID: 0375040; OID: NLM: PMC4606750 [Available on 11/01/16]; PMCR: 2016/11/01 00:00; 2015/08/21 [aheadofprint]; ppublish