Asthma Risk Among Individuals With Androgen Receptor Deficiency

Gaston, Benjamin; Marozkina, Nadzeya; Newcomb, Dawn C.; Sharifi, Nima; Zein, Joe

doi:10.1001/jamapediatrics.2021.0281

Cited by 12 publications

(4 citation statements)

References 7 publications

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“…The relation between blood levels of DHEA and lung function has also been observed in adolescents [21]. Interestingly, the beneficial role of androgens is supported by a registry study where subjects with the rare disease androgen insensitivity syndrome (AIS) had an increased risk of asthma [22]. The syndrome is caused by hereditary loss of androgen receptor (AR) function and the risk of asthma was less in those with AIS being treated with testosterone.…”

Section: Discussion (1702 Words [Original Submission 1652])mentioning

confidence: 93%

Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids

Yasinska,

Gómez,

Kolmert

et al. 2023

ERJ Open Res

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RationalePatients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail.ObjectivesTo measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.MethodsUrine collected at baseline in the U-BIOPRED study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study.Measurements and Main ResultsThe concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulphate (DHEA-S) concentrations were<5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high dose ICS only, were more suppressed in females than males (p-value <0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p-value <0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12–18 months.ConclusionThe pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.

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Section: Discussion (1702 Words [Original Submission 1652])mentioning

confidence: 93%

Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids

Yasinska,

Gómez,

Kolmert

et al. 2023

ERJ Open Res

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“…Recently, researchers also have found that AR could suppress allergic airway inflammation and improve lung function. 17,18 However, whether AR regulates the MAPK1 and MAPK14 in the epithelial cells of asthma is unclear.…”

Section: Screening Of the Key Genesmentioning

confidence: 99%

“…16 Recent studies have shown that high AR expression and high androgen levels in the bronchus are associated with better lung function, fewer symptoms and lower fractional exhaled nitric oxide in human asthma, and asthma prevalence is lower in men than in women. 17,18 Indeed, the AR-deficient mice increased the severity of antigen-induced airway inflammation and bronchoconstriction. 18 Therefore, the roles and mechanisms of AR should be considered in the asthma management.…”

Section: Introductionmentioning

confidence: 99%

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Androgen receptor suppresses inflammatory response of airway epithelial cells in allergic asthma through MAPK1 and MAPK14

Xia

Sun

2022

Hum Exp Toxicol

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Background Dysfunction of airway epithelial cells in patients with asthma is closely with the occurrence and development of allergic asthma. Finding the differences of airway epithelium between asthmatic patients and normal patients is helpful to find out new treatment strategies. Methods First, three original microarray datasets (GSE89809, GSE41861, GSE104468) from the Gene Expression Omnibus (GEO) dataset were used to assess differentially expressed genes in the epithelial tissues between patients with allergic asthma and healthy controls. Then, 10 ng/mL TGF-β1 treated BEAS-2B cells and rats with ovalbumin induced allergic asthma were performed to confirm our assumption from the gene expression analysis with microarrays. Results Top ten hub significant difference genes were obtained by Cytohubba plug-in from GSE41861, and found that androgen receptor (AR) was closely associated with the mitogen-activated protein kinase (MAPK) pathway, especially MAPK1 and MAPK14. After treated with the TGF-β1 treated BEAS-2B cells and rats with allergic asthma, we found that 5α-dihydrotestosterone (5α-DHT), AR agonist, significantly decreased the Th2 inflammation (IL-25 and IL-33), MAPK1 and MAPK14 proteins expression in vitro and in vivo. The roles of 5α-DHT were similar with the results of chicanine (a p38 MAPK and ERK1/2 inhibitor), but the roles of 5α-DHT were masked by the C16-PAF (a MAPK and MEK/ERK activator) treatment. Conclusion Androgen receptor limits the secretion of Th2 inflammatory factors by downregulating MAPK1 and MAPK14 in the TGF-β1 treated BEAS-2B cells and rats with ovalbumin induced allergic asthma, which plays a critical role for the therapeutics of patients with asthma.

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Gender differences and sex-related hormonal factors in asthma

Leynaert

Real

Idrose

et al. 2023

Asthma in the 21st Century

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Asthma Risk Among Individuals With Androgen Receptor Deficiency

Abstract: China), for editing assistance. We thank the health workers in the 220 counties of the 31 provinces for their strong collaboration and great efforts made as part of the National Free Preconception Health Examination Project. Dr Sheng was not compensated for his work.

Cited by 12 publications

References 7 publications

Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids

Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids

Androgen receptor suppresses inflammatory response of airway epithelial cells in allergic asthma through MAPK1 and MAPK14

Gender differences and sex-related hormonal factors in asthma

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