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

Card, Jeffrey W.; Voltz, James W.; Ferguson, Catherine D.; Carey, Michelle A.; DeGraff, Laura M.; Peddada, Shyamal D.; Morgan, Daniel L.; Zeldin, Darryl C.

doi:10.1152/ajplung.00407.2006

Cited by 46 publications

(44 citation statements)

References 32 publications

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“…Given that estrogen did not provide a protective benefit to female mice, we hypothesized that androgen may have exacerbated the response to bleomycin in this model, consistent with previous observations in a different model of lung disease (28). To test this hypothesis, lung function analysis was performed in castrated males as well as castrated males treated with exogenous DHT.…”

Section: Androgen Exacerbates Bleomycin-induced Lung Function Declinesupporting

confidence: 57%

Male Sex Hormones Exacerbate Lung Function Impairment after Bleomycin-Induced Pulmonary Fibrosis

Voltz¹,

Card²,

Carey³

et al. 2008

Am J Respir Cell Mol Biol

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104

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The roles of sex hormones as modulators of lung function and disease have received significant attention as differential sex responses to various lung insults have been recently reported. The present study used a bleomycin-induced pulmonary fibrosis model in C57BL/6 mice to examine potential sex differences in physiological and pathological outcomes. Endpoints measured included invasive lung function assessment, immunological response, lung collagen deposition, and a quantitative histological analysis of pulmonary fibrosis. Male mice had significantly higher basal static lung compliance than female mice (P , 0.05) and a more pronounced decline in static compliance after bleomycin administration when expressed as overall change or percentage of baseline change (P , 0.05). In contrast, there were no significant differences between the sexes in immune cell infiltration into the lung or in total lung collagen content after bleomycin. Total lung histopathology scores measured using the Ashcroft method did not differ between the sexes, while a quantitative histopathology scoring system designed to determine where within the lung the fibrosis occurred indicated a tendency toward more fibrosis immediately adjacent to airways in bleomycin-treated male versus female mice. Furthermore, castrated male mice exhibited a female-like response to bleomycin while female mice given exogenous androgen exhibited a male-like response. These data indicate that androgens play an exacerbating role in decreased lung function after bleomycin administration, and traditional measures of fibrosis may miss critical differences in lung function between the sexes. Sex differences should be carefully considered when designing and interpreting experimental models of pulmonary fibrosis in mice.

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Section: Androgen Exacerbates Bleomycin-induced Lung Function Declinesupporting

confidence: 57%

Male Sex Hormones Exacerbate Lung Function Impairment after Bleomycin-Induced Pulmonary Fibrosis

Voltz¹,

Card²,

Carey³

et al. 2008

Am J Respir Cell Mol Biol

Self Cite

104

View full text Add to dashboard Cite

show abstract

“…Specifically, greater increases in total respiratory system resistance, elastance, and other mechanical parameters were observed in males in response to methacholine aerosol (13). Subsequent studies revealed that this sex difference appears to be due to in vivo effects of androgens on vagus nerve-mediated reflex pathways and not to differences in innate responsiveness of airway smooth muscle (14). Airway responsiveness in castrated male mice to inhaled methacholine was equivalent to that in intact females, while females administered exogenous testosterone responded to inhaled methacholine in a fashion similar to that of intact males (14).…”

Section: Sex Differences In Respiratory Physiologymentioning

confidence: 96%

Hormonal Influences on Lung Function and Response to Environmental Agents: Lessons from Animal Models of Respiratory Disease

Card¹,

Zeldin²

2009

Proceedings of the American Thoracic Society

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Numerous studies in humans and experimental animals have identified considerable sex differences in respiratory physiology and in the response of the lung to environmental agents. These differences appear to be mediated, at least in part, by sex hormones and their nuclear receptors. Moreover, animal models are increasingly used to study pathogenic mechanisms and test potential therapies for a variety of human lung diseases, many of which appear to be influenced by sex and sex hormones. In this article, data are summarized from studies of lung function and disease in which sex differences have been observed. Specific attention is paid to animal models of acute lung injury, nonallergic and allergic lung inflammation, and lung fibrosis. It is anticipated that continued investigation of the role of sex and sex hormones in animal models will provide valuable insight into the pathogenesis and potential treatments for a variety of acute and chronic human lung diseases.

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“…Furthermore, it is important to consider whether and how progesterone influences ASM, given limited data of its effects on airway function and asthma (104,109,126,295). A similar question can be raised regarding a "protective" effect for testosterone acting via androgen receptors (33,36,37,158).…”

Section: Asm [Ca 2ϩ ] I and Contractilitymentioning

confidence: 99%

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

Prakash

2013

American Journal of Physiology-Lung Cellular and Molecular Phys

179

154

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Prakash YS. Airway smooth muscle in airway reactivity and remodeling: what have we learned? Am J Physiol Lung Cell Mol Physiol 305: L912-L933, 2013. First published October 18, 2013 doi:10.1152/ajplung.00259.2013.-It is now established that airway smooth muscle (ASM) has roles in determining airway structure and function, well beyond that as the major contractile element. Indeed, changes in ASM function are central to the manifestation of allergic, inflammatory, and fibrotic airway diseases in both children and adults, as well as to airway responses to local and environmental exposures. Emerging evidence points to novel signaling mechanisms within ASM cells of different species that serve to control diverse features, including 1) [Ca 2ϩ ]i contractility and relaxation, 2) cell proliferation and apoptosis, 3) production and modulation of extracellular components, and 4) release of pro-vs. anti-inflammatory mediators and factors that regulate immunity as well as the function of other airway cell types, such as epithelium, fibroblasts, and nerves. These diverse effects of ASM "activity" result in modulation of bronchoconstriction vs. bronchodilation relevant to airway hyperresponsiveness, airway thickening, and fibrosis that influence compliance. This perspective highlights recent discoveries that reveal the central role of ASM in this regard and helps set the stage for future research toward understanding the pathways regulating ASM and, in turn, the influence of ASM on airway structure and function. Such exploration is key to development of novel therapeutic strategies that influence the pathophysiology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis.

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

Abstract: Card JW, Voltz JW, Ferguson CD, Carey MA, DeGraff LM, Peddada SD, Morgan DL, Zeldin DC. Male sex hormones promote vagally mediated reflex airway responsiveness to cholinergic stimulation.

Cited by 46 publications

References 32 publications

Male Sex Hormones Exacerbate Lung Function Impairment after Bleomycin-Induced Pulmonary Fibrosis

Male Sex Hormones Exacerbate Lung Function Impairment after Bleomycin-Induced Pulmonary Fibrosis

Hormonal Influences on Lung Function and Response to Environmental Agents: Lessons from Animal Models of Respiratory Disease

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

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