Article

Spontaneous airway hyperresponsiveness in estrogen receptor-alpha-deficient mice.

Division of Intramural Research, NIH/NIEHS, Triangle Park, NC 27709, USA.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 11.99). 02/2007; 175(2):126-35. DOI: 10.1164/rccm.200509-1493OC
Source: PubMed

ABSTRACT 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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Available from: Vickie R Walker, Jul 07, 2015
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This was especially within the C3H-strain, hardly within the JF1-strain. Causal for the bigger gas exchange region of female compared to male individuals when related to the body weight is primarily an evolutionary advantage to support reproduction. During pregnancy and lactation more energy in form of oxygen is needed. There is a difference in the structural parameters, although the mice in this study have never been pregnant or lactating. This means that during pregnancy and lactation not only new lung tissue has to be developed but the utilisation of existing tissue can be optimised. An important motivation for this work was to ease the choice of laboratory animals in pulmonary research. The data gathered regarding the volumes of elastin and collagen may be especially helpful in the future research of emphysema, if the examined strains are going to be used.