title: Prolonged ovarian hormone deprivation alters the effects of 17β-estradiol on microRNA expression in the aged female rat hypothalamus.
abstract: Administration of 17β-estradiol (E2) has beneficial effects on cognitive function in peri- but not post-menopausal women, yet the molecular mechanisms underlying age-related changes in E2 action remain unclear. We propose that there is a biological switch in E2 action that occurs coincident with age and length of time after ovarian hormone depletion, and we hypothesized that age-dependent regulation of microRNAs (miRNAs) could be the molecular basis for that switch. Previously we showed that miRNAs are regulated by E2 in young compared to aged female rats. Here we tested whether increasing lengths of ovarian hormone deprivation in aged females altered E2 regulation of these mature miRNAs. In addition, we determined where along the miRNA biogenesis pathway E2 exerted its effects. Our results showed that age and increased lengths of ovarian hormone deprivation abolished the ability of E2 to regulate mature miRNA expression in the brain. Further, we show that E2 acted at specific points along the miRNA biogenesis pathway.
authors.affiliation: Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Yathindar S
authors.initials: YS
authors.lastname: Rao
authors.affiliation: Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Cody L
authors.initials: CL
authors.lastname: Shults
authors.affiliation: Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Pinceti
authors.affiliation: Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Toni R
authors.initials: TR
authors.lastname: Pak
mesh_terms: D000375:Aging; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D010052:Ovariectomy; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D004958:Estradiol
keywords: Gerotarget; aging; estrogen; hypothalamus; microRNA