title: Upregulation of estrogen receptor alpha and mediation of 17beta-estradiol vasoprotective effects via estrogen receptor alpha in basilar arteries in rats after experimental subarachnoid hemorrhage.
abstract: OBJECTIVE
  The authors previously demonstrated that 17beta-estradiol benzoate (E2) treatment prevents subarachnoid hemorrhage (SAH)-induced cerebral vasospasm and preserves endothelial nitric oxide synthase (eNOS) in male rats. Changes in the expression of estrogen receptor (ER) subtypes ERalpha and -beta and their roles in the E2-mediated preservation of eNOS in SAH remain unknown. In the present study the effects of SAH on the expression of ERalpha and -beta in the cerebral arteries were clarified, and the receptor roles in the E2-mediated preservation of eNOS expression in SAH were differentiated.
  
  
  METHODS
  A 2-hemorrhage SAH model was induced by 2 autologous blood injections into the cisterna magna of adult male rats. The effect of SAH on ERalpha and -beta expression was evaluated. Other rats subcutaneously received implanted Silastic tubes containing corn oil with E2 and daily injections of various doses of an ERalpha- (methyl-piperidinopyrazole [MPP]) or ERbeta-selective antagonist (R,R-tetrahydrochrysene) after the first hemorrhage. The protein levels of ERalpha, ERbeta, eNOS, and inducible nitric oxide synthase (iNOS) from basilar arteries were examined using Western blot analysis, and their mRNAs were evaluated by reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  The ERalpha but not the ERbeta was upregulated in the basilar artery after SAH. Treatment with MPP eliminated E2-mediated effects in SAH, relieved cerebral vasospasm, preserved eNOS expression, and suppressed iNOS expression.
  
  
  CONCLUSIONS
  Estrogen receptor alpha is upregulated in the basilar artery after SAH. Note that E2 exerts its protective effects through ERalpha-dependent pathways to relieve cerebral vasospasm and preserve eNOS expression. A selective ERalpha agonist may be the drug of choice for the treatment of patients with SAH.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Huei-Chuan
authors.initials: HC
authors.lastname: Shih
authors.forename: Chih-Lung
authors.initials: CL
authors.lastname: Lin
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Wu
authors.forename: Aij-Lie
authors.initials: AL
authors.lastname: Kwan
authors.forename: Yi-Ren
authors.initials: YR
authors.lastname: Hong
authors.forename: Shen-Long
authors.initials: SL
authors.lastname: Howng
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000378:metabolism; D001565:Benzoates / Q000627:therapeutic use*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000627:therapeutic use*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D001565:Benzoates; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D012333:RNA, Messenger; C514340:estradiol-17-benzoate; D004958:Estradiol; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat