Spontaneous Airway Hyperresponsiveness in Estrogen Receptor-α–deficient Mice

Carey, Michelle A.; Card, Jeffrey W.; Bradbury, J. Alyce; Moorman, Michael P.; Haykal-Coates, Najwa; Gavett, Stephen H.; Graves, Joan P.; Walker, Vickie R.; Flake, Gordon P.; Voltz, James W.; Zhu, Daling; Jacobs, Elizabeth R.; Dakhama, Azzeddine; Larsen, Gary L.; Loader, Joan E.; Gelfand, Erwin W.; Germolec, Dori R.; Korach, Kenneth S.; Zeldin, Darryl C.

doi:10.1164/rccm.200509-1493oc

Cited by 116 publications

(119 citation statements)

References 65 publications

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“…Importantly, we recently observed a considerable sex difference in murine airway responsiveness to cholinergic stimulation, as assessed by invasive measurement of respiratory mechanics, wherein the airways of naïve male C57BL/6 and BALB/c mice were found to be considerably more sensitive to methacholine aerosol than were those of naïve females (4). Furthermore, the minimal airway responsiveness of female mice to methacholine is not likely due to effects mediated by female sex hormones, as alteration of circulating levels via ovariectomy or exogenous administration of estradiol fails to alter responsiveness (5). At present, however, the potential for male sex hormones to influence airway responsiveness is unknown.…”

mentioning

confidence: 97%

Male sex hormones promote vagally mediated reflex airway responsiveness to cholinergic stimulation

Card¹,

Voltz²,

Ferguson³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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mentioning

confidence: 97%

Male sex hormones promote vagally mediated reflex airway responsiveness to cholinergic stimulation

Card¹,

Voltz²,

Ferguson³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Estrogen replacement therapy in ovariectomized mice also attenuates the development of airway dysfunction elicited by allergic airway inflammation (Dimitropoulou et al 2009). Additionally, female estrogen receptor alpha-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 a-deficient mice is associated with decreased CHRM2 expression and function (Carey et al 2007).…”

Section: Gonadsmentioning

confidence: 99%

“…Additionally, female estrogen receptor alpha-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 a-deficient mice is associated with decreased CHRM2 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).…”

Section: Gonadsmentioning

confidence: 99%

“…One the other hand, indirect evidences suggest that androgens foster contraction. For example, the spontaneously greater level of airway responsiveness observed in healthy male mice compared with females is eliminated by castration (Card et al 2007). Administration of testosterone to either females or castrated males also increases airway responsiveness to methacholine (Card et al 2007).…”

Section: Gonadsmentioning

confidence: 99%

“…Administration of testosterone to either females or castrated males also increases airway responsiveness to methacholine (Card et al 2007). The sex disparities in airway responsiveness and the potentiating effect of testosterone on airway responsiveness are abrogated by bilateral vagotomy, suggesting that testosterone increases airway responsiveness indirectly in vivo by acting through the vagal nerves (Card et al 2007). …”

Section: Gonadsmentioning

confidence: 99%

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Endocrine regulation of airway contractility is overlooked

Bossé

2014

Journal of Endocrinology

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Asthma is a prevalent respiratory disorder triggered by a variety of inhaled environmental factors, such as allergens, viruses, and pollutants. Asthma is characterized by an elevated activation of the smooth muscle surrounding the airways, as well as a propensity of the airways to narrow excessively in response to a spasmogen (i.e. contractile agonist), a feature called airway hyperresponsiveness. The level of airway smooth muscle (ASM) activation is putatively controlled by mediators released in its vicinity. In asthma, many mediators that affect ASM contractility originate from inflammatory cells that are mobilized into the airways, such as eosinophils. However, mounting evidence indicates that mediators released by remote organs can also influence the level of activation of ASM, as well as its level of responsiveness to spasmogens and relaxant agonists. These remote mediators are transported through circulating blood to act either directly on ASM or indirectly via the nervous system by tuning the level of cholinergic activation of ASM. Indeed, mediators generated from diverse organs, including the adrenals, pancreas, adipose tissue, gonads, heart, intestines, and stomach, affect the contractility of ASM. Together, these results suggest that, apart from a paracrine mode of regulation, ASM is subjected to an endocrine mode of regulation. The results also imply that defects in organs other than the lungs can contribute to asthma symptoms and severity. In this review, I suggest that the endocrine mode of regulation of ASM contractility is overlooked.

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Inhalation Toxicology Methods: The Generation and Characterization of Exposure Atmospheres and Inhalational Exposures

Chen

Lippmann

2015

CP Toxicology

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In this review, we outline the need for laboratory-based inhalation toxicology studies, the historical background on adverse health effects of airborne toxicants, and the benefits of advance planning for the building of analytic options into the study design to maximize the scientific gains to be derived from the investments in the study. We then discuss methods for: 1) the generation and characterization of exposure atmospheres for inhalation exposures in humans and laboratory animals; 2) their delivery and distribution into and within whole-body exposure chambers, head-only exposure chambers, face-masks, and mouthpieces or nasal catheters; 3) options for on-line functional assays during and between exposures; and 4) options for serial non-invasive assays of response. In doing so, we go beyond exposures to single agents and simple mixtures, and include methods for evaluating biological responses to complex environmental mixtures. We also emphasize that great care should be taken in the design and execution of such studies so that the scientific returns can be maximized both initially, and in follow-up utilization of archived samples of the exposure atmospheres, excreta, and tissues collected for histology.

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Spontaneous Airway Hyperresponsiveness in Estrogen Receptor-α–deficient Mice

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

Cited by 116 publications

References 65 publications

Male sex hormones promote vagally mediated reflex airway responsiveness to cholinergic stimulation

Male sex hormones promote vagally mediated reflex airway responsiveness to cholinergic stimulation

Endocrine regulation of airway contractility is overlooked

Inhalation Toxicology Methods: The Generation and Characterization of Exposure Atmospheres and Inhalational Exposures

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