Trends in Endocrinology & Metabolism
ReviewIt's all about sex: gender, lung development and lung disease
Introduction
Lung disease kills over 349 000 Americans every year and more than 35 million Americans have chronic lung disease [American Lung Association (ALA) lung disease data 2006 (www.lungusa.org)]. Substantial epidemiological evidence suggests that gender affects the incidence, susceptibility and severity of several lung diseases. Many studies have addressed the role of hormones in the gender disparities of pulmonary conditions. Some studies point to developmental and physiological differences playing roles. We will first review evidence for gender differences in lung development and then address gender differences in the prevalence and severity of several lung diseases using data from both human and animal studies.
Section snippets
Lung development
Sex hormones appear to exert regulatory effects on human lung development before and during the neonatal period. The androgen receptor is expressed in mesenchymal and epithelial cells of the lung throughout the human lifespan [1], and branching morphogenesis of human lung might be regulated in part by androgens [1]. Estrogen receptors α and β (ERα and ERβ) are also expressed in human lung [2]. Gender differences are also manifested in the expression of key genes. For example, surfactant
Interstitial lung diseases and idiopathic pulmonary arterial hypertension
There are gender differences in the prevalence of interstitial lung diseases. Idiopathic pulmonary fibrosis (see Glossary) is more prevalent in men than in women 14, 15 (Figure 1a), but whether this difference is directly due to or modified by sex hormone effects is unclear. Lymphangiomyomatosis (LAM) is a rare pulmonary condition primarily affecting young women of childbearing age [16]. Various anti-estrogen strategies have been used in the treatment of LAM and, currently, progesterone is the
Asthma
Evidence from several studies suggests a role for sex hormones in the pathogenesis of asthma. Among the general population, asthma prevalence is higher in women than in men [27]. However, several clinical studies point to distinctive changes in the prevalence and severity of asthma with age. Male children have asthma more frequently than do female children 28, 29. However, in and around the time of puberty, there is a reversal of this incidence leading to a female predominance [29]. Later in
Lung cancer
While lung cancer mortality in men appears to have reached a plateau, the mortality rate in women has increased considerably in the past 30 years, increasing fourfold since 1970 [55]. However, rates of diagnoses and deaths from lung cancer are still greater in men than in women (Figure 1c). Although cigarette smoking is certainly the primary cause of lung cancer, an estimated 15 000 lung cancer deaths per year occur in individuals who have never smoked [56]. Among these individuals who have
Summary
Gender plays a major role in both the healthy and diseased lung from very early life onwards. As summarized in Figure 2, sex hormones exert regulatory effects on lung development, physiology and pathology. Gender also affects airway inflammation and the prevalence and severity of many major lung diseases including pulmonary fibrosis, asthma and lung cancer (Figure 2). The gender differences discussed in this review highlight the importance of considering sex hormones in the prevention,
Acknowledgements
The authors would like to thank Drs Michael Fessler and Patricia Chulada for helpful comments during the preparation of this manuscript. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. J.W.C. is the recipient of a Senior Research Training Fellowship from the American Lung Association of North Carolina.
Glossary
- Airway hyperresponsiveness
- an increased sensitivity of the airways to an inhaled constrictor agonist and a characteristic feature of asthma
- Bleomycin
- an antibiotic produced by the bacterium Streptomyces verticillus used as an anti–cancer agent. The most serious complication of bleomycin is pulmonary fibrosis. It is used to induce experimental fibrosis in laboratory animals.
- COPD
- chronic obstructive pulmonary disease (COPD) is a group of diseases characterized by limitation of airflow that is not
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