title: Roles of estrogen in the formation of intracranial aneurysms in ovariectomized female mice.
abstract: BACKGROUND
  Epidemiological studies have indicated that postmenopausal women have a higher incidence of intracranial aneurysms than men in the same age group.
  
  
  OBJECTIVE
  To investigate whether estrogen or estrogen receptors (ERs) mediate protective effects against the formation of intracranial aneurysms.
  
  
  METHODS
  Intracranial aneurysms were induced in mice by combining a single injection of elastase into the cerebrospinal fluid with deoxycorticosterone acetate salt hypertension. The mice were treated with estrogen (17β-estradiol), an ERα agonist (propyl pyrazole triol), and an ERβ agonist (diarylpropionitrile) with and without a nitric oxide synthase inhibitor.
  
  
  RESULTS
  The ovariectomized female mice had a significantly higher incidence of aneurysms than the male mice, which was consistent with findings in previous epidemiological studies. In ovariectomized female mice, an ERβ agonist, but not an ERα agonist or 17β-estradiol, significantly reduced the incidence of aneurysms. The protective effect of the ERβ agonist was absent in the ovariectomized ERβ knockout mice. The protective effect of the ERβ agonist was negated by treatment with a nitric oxide synthase inhibitor.
  
  
  CONCLUSIONS
  The effects of sex, menopause, and estrogen treatment observed in this animal study were consistent with previous epidemiological findings. Stimulation of estrogen receptor-β was protective against the formation of intracranial aneurysms in ovariectomized female mice.
authors.affiliation: ‡Department of Anesthesia and Perioperative Care, §Department of Neurological Surgery, University of California, San Francisco, California; ¶Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa; ‖Department of Neurosurgery, School of Medicine, University of Tokushima, Tokushima City, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Tada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Makino
authors.forename: Hajime
authors.initials: H
authors.lastname: Furukawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimada
authors.forename: Kosuke
authors.initials: K
authors.lastname: Wada
authors.forename: Elena I
authors.initials: EI
authors.lastname: Liang
authors.forename: Shoko
authors.initials: S
authors.lastname: Murakami
authors.forename: Mari
authors.initials: M
authors.lastname: Kudo
authors.forename: David K
authors.initials: DK
authors.lastname: Kung
authors.forename: David M
authors.initials: DM
authors.lastname: Hasan
authors.forename: Keiko T
authors.initials: KT
authors.lastname: Kitazato
authors.forename: Shinji
authors.initials: S
authors.lastname: Nagahiro
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lawton
authors.forename: Tomoki
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists; D047629:Estrogen Receptor beta / Q000819:agonists*; D004967:Estrogens; D005260:Female; D002532:Intracranial Aneurysm / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009570:Nitriles / Q000494:pharmacology; D010052:Ovariectomy; D010636:Phenols; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012727:Sex Characteristics
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D004958:Estradiol