title: Spontaneous airway hyperresponsiveness in estrogen receptor-alpha-deficient mice.
abstract: BACKGROUND
  Airway hyperresponsiveness is a critical feature of asthma. Substantial epidemiologic evidence supports a role for female sex hormones in modulating lung function and airway hyperresponsiveness in humans.
  
  
  OBJECTIVE
  To examine the role of estrogen receptors in modulating lung function and airway responsiveness using estrogen receptor-deficient mice.
  
  
  METHODS
  Lung function was assessed by a combination of whole-body barometric plethysmography, invasive measurement of airway resistance, and isometric force measurements in isolated bronchial rings. M2 muscarinic receptor expression was assessed by Western blotting, and function was assessed by electrical field stimulation of tracheas in the presence/absence of gallamine. Allergic airway disease was examined after ovalbumin sensitization and exposure.
  
  
  RESULTS
  Estrogen receptor-alpha knockout mice exhibit a variety of lung function abnormalities and have enhanced airway responsiveness to inhaled methacholine and serotonin under basal conditions. This is associated with reduced M2 muscarinic receptor expression and function in the lungs. Absence of estrogen receptor-alpha also leads to increased airway responsiveness without increased inflammation after allergen sensitization and challenge.
  
  
  CONCLUSIONS
  These data suggest that estrogen receptor-alpha is a critical regulator of airway hyperresponsiveness in mice.
authors.affiliation: Division of Intramural Research, NIH/NIEHS, Triangle Park, NC 27709, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Carey
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Card
authors.forename: J Alyce
authors.initials: JA
authors.lastname: Bradbury
authors.forename: Michael P
authors.initials: MP
authors.lastname: Moorman
authors.forename: Najwa
authors.initials: N
authors.lastname: Haykal-Coates
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gavett
authors.forename: Joan P
authors.initials: JP
authors.lastname: Graves
authors.forename: Vickie R
authors.initials: VR
authors.lastname: Walker
authors.forename: Gordon P
authors.initials: GP
authors.lastname: Flake
authors.forename: James W
authors.initials: JW
authors.lastname: Voltz
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Jacobs
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Gary L
authors.initials: GL
authors.lastname: Larsen
authors.forename: Joan E
authors.initials: JE
authors.lastname: Loader
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
authors.forename: Dori R
authors.initials: DR
authors.lastname: Germolec
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Korach
authors.forename: Darryl C
authors.initials: DC
authors.lastname: Zeldin
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000485:Allergens / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004594:Electrophysiology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology*; D004967:Estrogens / Q000097:blood; D005260:Female; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D010525:Peripheral Nerves / Q000502:physiology; D010991:Plethysmography; D043585:Receptor, Muscarinic M2 / Q000032:analysis / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D012701:Serotonin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology
chemical_list: D000485:Allergens; D016207:Cytokines; D047628:Estrogen Receptor alpha; D004967:Estrogens; D043585:Receptor, Muscarinic M2; D016210:Methacholine Chloride; D012701:Serotonin; D010047:Ovalbumin; D000109:Acetylcholine