Life stress and diminished expression of genes encoding glucocorticoid receptor and β₂-adrenergic receptor in children with asthma

Despite evidence that stressful experience can exacerbate the symptoms of asthma, little is known about the biological mechanisms through which this occurs. This study examined whether life stress reduces expression of the genes coding for the glucocorticoid receptor and the β₂-adrenergic receptor. A total of 77 children were enrolled in the study (59% male; mean age, 13.5 years). Thirty-nine of them were physician-diagnosed with asthma, and 38 were healthy. After an in-depth interview regarding stressful experiences, leukocytes were collected through antecubital venipuncture, and real-time RT-PCR was used to quantify mRNA. Chronic stress was associated with reduced expression of mRNA for the β₂-adrenergic receptor among children with asthma. In the sample of healthy children, however, the direction of this effect was reversed. The occurrence of a major life event in the 6 months before the study was not sufficient to influence patterns of gene expression. When such events occurred in the context of a chronic stressor, however, their association with patterns of gene expression was accentuated. Children with asthma who simultaneously experienced acute and chronic stress exhibited a 5.5-fold reduction in glucocorticoid receptor mRNA and a 9.5-fold reduction in β₂-adrenergic receptor mRNA relative to children with asthma without comparable stressor exposure. These findings suggest that stressful experience diminishes expression of the glucocorticoid and β₂- adrenergic receptor genes in children with asthma. To the extent that it diminishes sensitivity to the antiinflammatory properties of glucocorticoids or the bronchodilatory properties of β-agonists, this process could explain the increased asthma morbidity associated with stress.