Glucocorticoid receptor expression on circulating leukocytes in healthy and asthmatic adolescents in response to exercise

Abstract

BackgroundPoor aerobic fitness is associated with worsening of asthma symptoms and fitness training may improve asthma control. The mechanism linking fitness with asthma is not known. We hypothesized that repeated bouts of exercise would lead to a downregulation of glucocorticoid receptor (GR) expression on circulating leukocytes reflecting a reduced responsiveness to stress.MethodsIn a prospective exercise training intervention of healthy and asthmatic adolescents, GR expression in leukocytes was measured using flow cytometry in response to a brief exercise challenge before and after the training intervention. PBMC gene expression of GR, GRβ, HSP70, and TGFβ1, 2 were determined using RT-PCR.ResultsPeak V̇O2 increased by 14.6 ± 2.3% indicating an effective training (p<0.01). There was a significant difference in GR expression among leukocyte subtypes, with highest expression in eosinophils. Following the training intervention, there was a significant decrease in baseline GR expression (p<0.05) in leukocyte and monocyte subtypes in both healthy and asthmatic adolescents.ConclusionsThis is the first study in adolescents to show that exercise training reduces GR expression on circulating leukocytes. We speculate that exercise training downregulates the stress response in general, manifested by decreased GR expression, and may explain why improving fitness improves asthma health.

Defining a role for exercise training in the management of asthma

“…Changes in the interactions between reactive oxygen species in healthy humans undergoing exercise intervention have been demonstrated [57], but this is yet to be investigated in adults with asthma. Additionally, mechanistic involvement of the glucocorticoid receptor does not necessarily fit with the findings of LU et al [38] when investigating he effect of exercise on glucocorticoid receptor expression in adolescents.…”

“…High-intensity interval training in children demonstrates an improvement in body mass index (BMI) and aerobic fitness but without improving inflammation as assessed by F eNO [41]. The most mechanistic work to date was undertaken in adolescents, and demonstrated that exercise training reduced glucocorticoid receptor expression in leukocytes and monocytes [38]. The authors postulated that exercise training reduced the stress response overall, resulting in a reduction in glucocorticoid receptor expression in several lymphocyte subsets after an acute exercise challenge and sustained after an exercise training intervention.…”

Low fitness and increased sedentary time are associated with worse asthma—The National Youth Fitness Survey

“…Large longitudinal studies have shown that childhood asthma is associated with reduced pulmonary function that tracks into adulthood 16 ; however, how fitness and sedentary time in young children affect asthma outcomes, including lung function in adults, is unknown. While the underlying mechanism(s) of improving fitness on asthma is unknown, a growing number of animal models and human studies suggest that aerobic exercise reduces airway remodeling, proinflammatory cytokines/responses including glucocorticoid receptor expression, and enhances regulatory T cell responses 39–41 . Interventions targeting increased physical activity and decreasing sedentary time may be more effective in younger children, who have less autonomy and control of their external environment 42 …”

The role of the human hypothalamus-pituitary-adrenocortical system in adaptation to physical exercise

“…Одним из возможных механизмов изменения чувствительности тканей к глюкокортикоидам может быть появление вариаций в количестве и чувствительности глюкокортикоидных рецепторов. Регулярные тренировки приводят к уменьшению в клетках крови экспрессии ГР во время отдыха (Bonifazi et al 2009;Lu et al 2017;Sousa e Silva et al 2010). Показано, что в покое, на фоне одинаковых базальных уровней АКТГ, КЛ и кортизолсвязывающего глобулина в плазме, высококвалифицированные пловцы имеют в 10 раз, а низко тренированные бегуны в 2 раза меньшую экспрессию мРНК ГРα в мононуклеарных клетках периферической крови, чем нетренированные субъекты (Bonifazi et al 2009).…”

“…Показано, что в покое, на фоне одинаковых базальных уровней АКТГ, КЛ и кортизолсвязывающего глобулина в плазме, высококвалифицированные пловцы имеют в 10 раз, а низко тренированные бегуны в 2 раза меньшую экспрессию мРНК ГРα в мононуклеарных клетках периферической крови, чем нетренированные субъекты (Bonifazi et al 2009). У подростков также было показано, что не только длительные, но и острые 30-минутные упражнения снижают экспрессию ГР в моноцитах, нейтрофилах, эозинофилах и базофилах через 1 час после окончания упражнений (Lu et al 2017).…”