title: Reproductive senescence blunts response of estrogen receptor-α expression to estrogen treatment in rat post-ischemic cerebral microvessels.
abstract: BACKGROUND
  Several studies demonstrate that estrogen treatment improves cerebral blood flow in ischemic brain regions of young ovariectomized (OVX) rats. Estrogen receptor-α (ER-α) may mediate estrogen's beneficial actions via its effects on the cerebral microvasculature. However, estrogen-derived benefit may be attenuated in aged, reproductively senescent (RS) rats. Our goal was to determine the effects of aging, estrogen deprivation and estrogen repletion with oral conjugated estrogens (CE) on postischemic cerebral microvascular protein expression of ER-α and ER-β.
  
  
  METHODS
  Fisher-344 (n = 37) female rats were randomly divided into the following groups: OVX, OVX CE-treated, RS untreated, and RS CE-treated. After 30 days pretreatment with CE (0.01 mg/kg) rats were subjected to 15 min. transient global cerebral ischemia. Non-ischemic naïve, OVX and RS rats were used as controls. Expression of ER-α and ER-β in isolated cortical cerebral microvessels (20 to 100 µm in diameter) was assessed using Western blot and immunohistochemistry techniques.
  
  
  RESULTS
  Age and reproductive status blunted nonischemic ER-α expression in microvessels of OVX rats (0.31 ± 0.05) and RS rats (0.33 ± 0.06) compared to naïve rats (0.45 ± 0.02). Postischemic microvascular expression of ER-α in OVX rats (0.01 ± 0.0) was increased by CE treatment (0.04 ± 0.01). Expression of ER-α in microvessels of RS rats (0.03 ± 0.02) was unaffected by CE treatment (0.01 ± 0.02). Western blot data are presented as a ratio of ER-α or ER-β proteins to β-actin and. Oral CE treatment had no effect on ER-β expression in postischemic microvessels of OVX and RS rats. Statistical analysis was performed by One-Way ANOVA and a Newman-Keuls or Student's post-hoc test.
  
  
  CONCLUSIONS
  Chronic treatment with CE increases ER-α but not ER-β expression in cerebral microvessels of OVX rats. Aging appears to reduce the normal ability of estrogen to increase ER-α expression in postischemic cerebral microvessels.
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors.forename: Emil
authors.initials: E
authors.lastname: Zeynalov
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors.forename: Niloofar
authors.initials: N
authors.lastname: Rezvani
authors.affiliation: Johns Hopkins University School of Medicine, Department of Anesthesiology and Critical Care Medicine, Baltimore, Maryland, United States of America.
authors.forename: Chikao
authors.initials: C
authors.lastname: Miyazaki
authors.affiliation: Johns Hopkins University School of Medicine, Department of Anesthesiology and Critical Care Medicine, Baltimore, Maryland, United States of America.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors.forename: Marguerite T
authors.initials: MT
authors.lastname: Littleton-Kearney
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000096:biosynthesis* / Q000378:metabolism; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D006801:Humans; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D051381:Rats
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004966:Estrogens, Conjugated (USP)