Modulatory role of endogenous androgens on airway smooth muscle tone in isolated guinea-pig and bovine trachea; involvement of β2-adrenoceptors, the polyamine system and external calcium

Bordallo, Javier; Boto, María José García de; Meana, Clara; Velasco, Lucía; Bordallo, Carmen; Suárez, Lorena; Cantabrana, Begoña; Sánchez, Manuel

doi:10.1016/j.ejphar.2008.10.039

Cited by 33 publications

(35 citation statements)

References 48 publications

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“…As guinea pig models can provide some of the essential features of human asthma, we have established that the androgen-induced relaxation of isolated trachea of guinea pigs and rabbits (Kouloumenta et al 2006, Bordallo et al 2008) is consistent with the results of the present in vivo studies, which is, to our knowledge, the first evidence of the bronchodilating effect elicited by androgens in an in vivo model of allergic asthma. Androgens actually diminished the bronchospasm induced by an antigenic challenge in guinea pigs sensitized with OVA.…”

Section: Bronchospasm Prevention By Androgenssupporting

confidence: 87%

“…Using male rabbit tracheal strips, it was found that TES and TES-BSA induce a slight relaxation on the acetylcholine-induced contraction which seems to be partially mediated through epithelium and nitric oxide (NO; Kouloumenta et al 2006). Similarly, in male guinea pig and bovine tracheal rings and strips, the 5a-reduced metabolite of TES, 5a-dihydrotestosterone (5a-DHT), produces substantial nongenomic relaxation on carbachol (CCh)-and KClinduced contraction (Bordallo et al 2008); these relaxations are epithelium independent, contrasting with the study of Kouloumenta et al (2006). In addition, Bordallo et al (2008) also found the first clue that the relaxant effect elicited by 5a-DHT might be attributed to voltage-gated L-type Ca 2C channel blockade.…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, in male guinea pig and bovine tracheal rings and strips, the 5a-reduced metabolite of TES, 5a-dihydrotestosterone (5a-DHT), produces substantial nongenomic relaxation on carbachol (CCh)-and KClinduced contraction (Bordallo et al 2008); these relaxations are epithelium independent, contrasting with the study of Kouloumenta et al (2006). In addition, Bordallo et al (2008) also found the first clue that the relaxant effect elicited by 5a-DHT might be attributed to voltage-gated L-type Ca 2C channel blockade. Indeed, the findings of these two pioneer studies have revealed that androgeninduced relaxation on ASM is nongenomically mediated, but the role of epithelium is yet unclear, and the limited in vitro data do not provide any solid indication about the site of the relaxing action of androgens.…”

Section: Introductionmentioning

confidence: 99%

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Androgens are bronchoactive drugs that act by relaxing airway smooth muscle and preventing bronchospasm

Montaño¹,

Espinoza²,

Flores‐Soto³

et al. 2014

Journal of Endocrinology

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Changes in the androgen levels in asthmatic men may be associated with the severity of asthma. Androgens induce a nongenomic relaxation in airway smooth muscle, but the underlying mechanisms remain unclear. The aim of this study was to investigate the potential bronchorelaxing action of testosterone (TES) and its metabolites (5a-and 5b-dihydrotestosterone (DHT). A preventive effect on ovalbumin (OVA)-induced bronchospasm was observed in sensitized guinea pigs for each androgen. Androgens were studied in response to bronchoconstrictors: carbachol (CCh) and KCl in isolated trachea rings with and without epithelium from non-sensitized and sensitized animals as well as on OVA-induced contraction. Androgens concentration-dependently abolished the contraction in response to CCh, KCl, and OVA. There were significant differences in the sensitivity to the relaxation induced by each androgen. 5b-DHT was more potent for relaxing KCl-induced contraction, while TES and 5a-DHT were more potent for CCh-and OVA-induced contraction. No differences were found in preparations with and without epithelium or in the presence of a nitric oxide (NO) synthase inhibitor or an inhibitor of K C channels. These data indicate the absence of involvement of the epithelium-, NO-and K C channels-dependent pathway in androgen-induced relaxation. However, in dissociated tracheal myocytes loaded with the calcium-binding fluorescent dye Fura -2, physiological concentrations of androgens decreased the KCl-induced [Ca 2C ] i increment. 5b-DHT was the most potent at decreasing KCl-induced [Ca 2C ] i increment and preventing bronchospasm. We suggest that androgen-induced brochorelaxation was mediated via decreased Ca 2C influx through L-type Ca 2C channels but additional Ca 2C entry blockade may be involved. Molecular changes in androgen structure may determine its preferential site of action. Key Words" asthma " testosterone " 5a-dihydrotestosterone" 5b-dihydrotestosterone " bronchoactive steroids " airway smooth muscle

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Section: Bronchospasm Prevention By Androgenssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Androgens are bronchoactive drugs that act by relaxing airway smooth muscle and preventing bronchospasm

Montaño¹,

Espinoza²,

Flores‐Soto³

et al. 2014

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Androgens Androgens, such as testosterone, have an acute, non-genomic, and non-estrogenic effect on ASM activation (Kouloumenta et al 2006, Bordallo et al 2008, Montano et al 2014. The direction of the effect depends on the state of ASM activation.…”

Section: Gonadsmentioning

confidence: 99%

“…The direction of the effect depends on the state of ASM activation. On one hand, androgens relax pre-contracted ASM (Kouloumenta et al 2006, Bordallo et al 2008, Montano et al 2014 and potentiate the relaxing effect of b 2 -agonists (Foster et al 1983, Bordallo et al 2008, which suggest an overall bronchodilator effect. On the other hand, in the same ASM preparations and at the same concentrations, androgens potentiate the contractile response to a spasmogen, which suggest a constrictor effect (Bordallo et al 2008).…”

Section: Gonadsmentioning

confidence: 99%

Endocrine regulation of airway contractility is overlooked

Bossé

2014

Journal of Endocrinology

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Asthma is a prevalent respiratory disorder triggered by a variety of inhaled environmental factors, such as allergens, viruses, and pollutants. Asthma is characterized by an elevated activation of the smooth muscle surrounding the airways, as well as a propensity of the airways to narrow excessively in response to a spasmogen (i.e. contractile agonist), a feature called airway hyperresponsiveness. The level of airway smooth muscle (ASM) activation is putatively controlled by mediators released in its vicinity. In asthma, many mediators that affect ASM contractility originate from inflammatory cells that are mobilized into the airways, such as eosinophils. However, mounting evidence indicates that mediators released by remote organs can also influence the level of activation of ASM, as well as its level of responsiveness to spasmogens and relaxant agonists. These remote mediators are transported through circulating blood to act either directly on ASM or indirectly via the nervous system by tuning the level of cholinergic activation of ASM. Indeed, mediators generated from diverse organs, including the adrenals, pancreas, adipose tissue, gonads, heart, intestines, and stomach, affect the contractility of ASM. Together, these results suggest that, apart from a paracrine mode of regulation, ASM is subjected to an endocrine mode of regulation. The results also imply that defects in organs other than the lungs can contribute to asthma symptoms and severity. In this review, I suggest that the endocrine mode of regulation of ASM contractility is overlooked.

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Sex Steroids Influence Brain-Derived Neurotropic Factor Secretion From Human Airway Smooth Muscle Cells

et al. 2015

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Brain derived neurotropic factor (BDNF) is emerging as an important player in airway inflammation, remodeling, and hyperreactivity. Separately, there is increasing evidence that sex hormones contribute to pathophysiology in the lung. BDNF and sex steroid signaling are thought to be intricately linked in the brain. There is currently little information on BDNF and sex steroid interactions in the airway, but is relevant to understanding growth factor signaling in the context of asthma in men vs. women. In this study, we assessed the effect of sex steroids on BDNF expression and secretion in human airway smooth muscle (ASM). Human ASM was treated with estrogen (E2) or testosterone (T, 10nM each) and intracellular BDNF and secreted BDNF measured. E2 and T significantly reduced secretion of BDNF; effects prevented by estrogen and androgen receptor inhibitor, ICI 182,780 (1uM) and flutamide (10uM), respectively. Interestingly, no significant changes were observed in intracellular BDNF mRNA or protein expression. High affinity BDNF receptor, TrkB, was not altered by E2 or T. E2 (but not T) significantly increased intracellular cyclic AMP levels. Notably, Epac1 and Epac2 expression were significantly reduced by E2 and T. Furthermore, SNARE complex protein SNAP25 was decreased. Overall, these novel data suggest that physiologically relevant concentrations of E2 or T inhibit BDNF secretion in human ASM, suggesting a potential interaction of sex steroids with BDNF in the airway that is different from brain. The relevance of sex steroid-BDNF interactions may lie in their overall contribution to airway diseases such as asthma.

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Modulatory role of endogenous androgens on airway smooth muscle tone in isolated guinea-pig and bovine trachea; involvement of β2-adrenoceptors, the polyamine system and external calcium

Cited by 33 publications

References 48 publications

Androgens are bronchoactive drugs that act by relaxing airway smooth muscle and preventing bronchospasm

Androgens are bronchoactive drugs that act by relaxing airway smooth muscle and preventing bronchospasm

Endocrine regulation of airway contractility is overlooked

Sex Steroids Influence Brain-Derived Neurotropic Factor Secretion From Human Airway Smooth Muscle Cells

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