In vivo modulation of glucocorticoid receptor mRNA by inhaled fluticasone propionate in bronchial mucosa and blood lymphocytes in subjects with mild asthma

Background: In vivo regulation of the glucocorticoid receptor (GR) by gluco corticoids provides a means of modulating sensitivity of targeted cells. Objective: We sought to determine the in vivo modulation of GR mRNA express ion by fluticasone propionate (FP) in subjects with mild asthma. Methods: Ten atopic asthmatic subjects were treated with FP 250 mu g twice daily for 4 weeks. Before and after treatment, the patients underwent fiber optic bronchoscopy with endobronchial biopsy and sampling of venous blood f or measurements of GR mRNA levels, A solution hybridization assay was used for quantitative analysis of GR mRNA. In addition, a 24-hour urinary cortis ol excretion and an adrenocorticotropic hormone test before and after treat ment with FP were performed. Results: A high interindividual variation in GR mRNA expression was seen. H owever, we detected a significant reduction of the GR mRNA levels in the en dobronchial biopsy specimens after FP treatment (36.6 +/- 23.1 and 25.0 +/- 10.9 amol GR mRNA/mu g RNA, respectively; P < .01). In the peripheral bloo d lymphocytes an even more striking downregulation of the GR by its cognate ligand was documented (30.3 +/- 26.5 and 8.8 +/- 5 amol GR mRNA/mu g RNA, respectively; P < .001), possibly reflecting differences in glucocorticoid sensitivity between tissues. A small but significant reduction of the 24-ho ur urinary cortisol excretion was observed (233 +/- 109 and 157 +/- 66 nmol /L, respectively; P < .01), whereas the feedback regulation of glucocortico id synthesis by means of the hypothalamic-pituitary-adrenal axis as assesse d by the adrenocorticotropic hormone test remained normal after treatment w ith FP. Conclusion: The results in this study confirm the potency of the inhaled co rticosteroid FP and provide evidence for a considerable tissue-specific int erindividual variation in the expression of the GR.