Science Inventory

SPONTANEOUS AIRWAY HYPERRESPONSIVENESS IN ESTROGEN RECEPTOR-A DEFICIENT MICE

Citation:

Carey, M. A., J. W. Card, J. A. Bradbury, M. P. Moorman, N HaykalCoates, S H. Gavett, J. P. Graves, V. R. Walker, G. P. FLAKE, J. W. VOLTZ, D. Zhu, E. R. Jacobs, A. Dakhama, G. Larsen, J. E. Loader, E. W. Gelfand, D. R. Germolec, K. S. Korach, AND D. Zeldin. SPONTANEOUS AIRWAY HYPERRESPONSIVENESS IN ESTROGEN RECEPTOR-A DEFICIENT MICE. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. American Thoracic Society, New York, NY, 175(2):126-135, (2007).

Impact/Purpose:

To examine the role of estrogen receptors in modulating lung function and airway responsiveness using estrogen receptor deficient mice.

Description:

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 following ovalbumin sensitization and exposure. Measurements and main results: Estrogen receptor-á 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-á also leads to increased airway responsiveness without increased inflammation following allergen sensitization and challenge.

Conclusions: These data suggest that estrogen receptor-á is a critical regulator of airway hyperresponsiveness in mice.

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Product Published Date: 01/03/2007
Record Last Revised: 08/09/2007
OMB Category: Other
Record ID: 104925