Spontaneous Airway Hyperresponsiveness in Estrogen Receptor-α–deficient Mice

Medical College of Wisconsin, Milwaukee, Wisconsin, United States
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 02/2007; 175(2):126-35. DOI: 10.1164/rccm.200509-1493OC
Source: PubMed


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.
To examine the role of estrogen receptors in modulating lung function and airway responsiveness using estrogen receptor-deficient mice.
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.
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.
These data suggest that estrogen receptor-alpha is a critical regulator of airway hyperresponsiveness in mice.

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    • "Additionally, female estrogen receptor-α-deficient mice are more sensitive to methacholine aerosol, either in the presence or the absence of allergic airway inflammation (Carey, et al. 2007). This hypercontractile phenotype in receptor-α-deficient mice is associated with decreased M 2 expression and function (Carey et al. 2007). Finally, low dose, but not high dose, of estrogens decreases airway responsiveness in ovariectomized rats in the absence of airway inflammation (Degano, et al. 2003). "
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