Faculty Collaboration Database

Spontaneous airway hyperresponsiveness in estrogen receptor-alpha-deficient mice. Am J Respir Crit Care Med 2007 Jan 15;175(2):126-35

Date

11/11/2006

Pubmed ID

17095746

Pubmed Central ID

PMC1899278

DOI

10.1164/rccm.200509-1493OC

Scopus ID

2-s2.0-33846286093 (requires institutional sign-in at Scopus site)   109 Citations

Abstract

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.

Author List

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

MESH terms used to index this publication - Major topics in bold

Acetylcholine
Allergens
Animals
Bronchial Hyperreactivity
Cytokines
Electrophysiology
Estrogen Receptor alpha
Estrogens
Female
Inflammation
Lung
Methacholine Chloride
Mice
Mice, Knockout
Ovalbumin
Peripheral Nerves
Plethysmography
Receptor, Muscarinic M2
Respiratory Hypersensitivity
Serotonin
Trachea