title: Aging and Loss of Circulating 17β-Estradiol Alters the Alternative Splicing of ERβ in the Female Rat Brain.
abstract: Loss of circulating 17β-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)β isoforms in the brain of female rats. Further, we tested whether changes in global transcriptional activity and splicing kinetics regulate the alternative splicing of ERβ. Our results revealed brain region-specific changes in ERβ alternative splicing in both aging and E2-deprivation paradigms and showed that ERβ 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 ERβ2 splice variant expression.
authors: Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153.
authors: Cody L
authors: CL
authors: Shults
authors: Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153.
authors: Elena
authors: E
authors: Pinceti
authors: Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153.
authors: Yathindar S
authors: YS
authors: Rao
authors: Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153.
authors: Toni R
authors: TR
authors: Pak
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004958:Estradiol / Q000097:blood*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D047629:Estrogen Receptor beta; D020033:Protein Isoforms; D004958:Estradiol