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Glucocorticoid receptor subunit expression in adenotonsillar tissue of children with obstructive sleep apnea
Aviv D Goldbart1, Maria C Veling, Julie L Goldman
1Department of Pediatrics, Kosair Children's Hospital Research Institute, University of Louisville, 570 South Preston Street, Suite 321, Louisville, KY 40202, USA.
Insights
Glucocorticoid receptors (GCR) are present in children's adenotonsillar tissue. Higher GCR-alpha expression in obstructive sleep apnea (OSA) patients suggests topical steroid therapy may benefit these children.
Area of Science:
- Pediatric Otolaryngology
- Molecular Biology
- Sleep Medicine
Background:
- Tonsillectomy and adenoidectomy (T&A) is common for pediatric obstructive sleep apnea (OSA).
- Topical steroid therapy may benefit children with OSA symptoms not meeting T&A criteria.
- Glucocorticoid receptor (GCR) expression in adenoid and tonsil tissue is uncharacterized.
Purpose of the Study:
- To investigate and compare the expression patterns of human GCR isoforms in pediatric adenotonsillar tissues.
- To determine if GCR expression differs between children with OSA and those with recurrent throat infections (RI).
Main Methods:
- Quantitative PCR, immunohistochemistry, and Western blotting were used to analyze GCR-alpha and GCR-beta expression.
- Adenotonsillar tissues from 36 children (OSA or RI) were analyzed.
- Specific primers and antibodies were employed for GCR isoforms.
Main Results:
- Both GCR-alpha and GCR-beta mRNA were detected in all adenotonsillar tissues, with GCR-alpha being more abundant.
- GCR-alpha mRNA expression was significantly higher in tissues from children with OSA compared to RI.
- Protein expression analysis confirmed higher GCR-alpha levels in OSA patients, with distinct topographic distribution patterns for both GCR isoforms.
Conclusions:
- Glucocorticoid receptors (GCR-alpha and GCR-beta) are expressed in pediatric adenotonsillar tissues.
- Increased GCR-alpha expression in OSA patients suggests potential efficacy of topical steroid treatment.
- The high GCR-alpha to GCR-beta ratio supports topical steroid therapy for children with adenotonsillar hypertrophy and snoring.
Abstract:
Tonsillectomy and adenoidectomy (T&A) is a frequent surgical procedure in children with obstructive sleep apnea (OSA). Many symptomatic children who do not fulfill the currently recommended criteria for T&A may benefit from topical intranasal steroid therapy. However, the expression of glucocorticoid receptor (GCR) expression in adenoid and tonsillar tissue is currently unknown. The objective of this study was to assess and compare expression patterns of the human GCR in children who undergo T&A for either recurrent throat infections (RI) or OSA. Adenotonsillar tissues from 36 children with OSA or RI were subjected to quantitative PCR using specific primers for GCR-alpha and GCR-beta and to immunohistochemistry and Western blotting for protein expression of GCR isoforms. mRNA encoding for expression of both GCR-alpha and GCR-beta was detected in the tonsils and adenoids of all children, with markedly higher relative abundance of the GCR-alpha. Furthermore, GCR-alpha mRNA expression was increased in OSA-derived adenoid and tonsil tissues compared with RI, whereas no differences emerged for GCR-beta. Immunoblots confirmed these findings for the protein transcripts of these genes, and immunohistochemistry showed a specific topographic pattern of distribution for both receptors in tonsillar tissue. GCR-alpha and GCR-beta are expressed in pediatric adenotonsillar tissue, are more abundant in OSA patients, and demonstrate a specific topographic pattern of expression. These findings along with the high GCR-alpha:GCR-beta ratio suggest a favorable profile for topical steroid therapy in snoring children with adenotonsillar hypertrophy.
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