- Comment in:
-
Am J Respir Crit Care Med. 2007 Jul 15;176(2):215; author reply 215-6.
Spontaneous airway hyperresponsiveness in estrogen receptor-alpha-deficient mice.
Carey MA,
Card JW,
Bradbury JA,
Moorman MP,
Haykal-Coates N,
Gavett SH,
Graves JP,
Walker VR,
Flake GP,
Voltz JW,
Zhu D,
Jacobs ER,
Dakhama A,
Larsen GL,
Loader JE,
Gelfand EW,
Germolec DR,
Korach KS,
Zeldin DC.
Division of Intramural Research, NIH/NIEHS, Triangle Park, NC 27709, USA.
RATIONALE: 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. OBJECTIVES: 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. MEASUREMENTS AND MAIN 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.
PMID: 17095746 [PubMed - indexed for MEDLINE]
PMCID: PMC1899278