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Androgens are bronchoactive drugs that act by relaxing airway smooth muscle and preventing bronchospasm.
J Endocrinol. 2014 Jul; 222(1):1-13.JE

Abstract

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 (5α- and 5β-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. 5β-DHT was more potent for relaxing KCl-induced contraction, while TES and 5α-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(+) channels. These data indicate the absence of involvement of the epithelium-, NO- and K(+) 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(2+)]i increment. 5β-DHT was the most potent at decreasing KCl-induced [Ca(2+)]i increment and preventing bronchospasm. We suggest that androgen-induced brochorelaxation was mediated via decreased Ca(2+) influx through L-type Ca(2+)channels but additional Ca(2+) entry blockade may be involved. Molecular changes in androgen structure may determine its preferential site of action.

Authors+Show Affiliations

Departamento de Biología Celular y FisiologíaInstituto de Investigaciones BiomédicasDepartamento de FarmacologíaFacultad de Medicina, Universidad Nacional Autónoma de México, Mexico, Distrito Federal 04510, MexicoDepartamento de Investigación en Hiperreactividad BronquialInstituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico, Distrito Federal, Mexico.Departamento de Biología Celular y FisiologíaInstituto de Investigaciones BiomédicasDepartamento de FarmacologíaFacultad de Medicina, Universidad Nacional Autónoma de México, Mexico, Distrito Federal 04510, MexicoDepartamento de Investigación en Hiperreactividad BronquialInstituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico, Distrito Federal, Mexico.Departamento de Biología Celular y FisiologíaInstituto de Investigaciones BiomédicasDepartamento de FarmacologíaFacultad de Medicina, Universidad Nacional Autónoma de México, Mexico, Distrito Federal 04510, MexicoDepartamento de Investigación en Hiperreactividad BronquialInstituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico, Distrito Federal, Mexico.Departamento de Biología Celular y FisiologíaInstituto de Investigaciones BiomédicasDepartamento de FarmacologíaFacultad de Medicina, Universidad Nacional Autónoma de México, Mexico, Distrito Federal 04510, MexicoDepartamento de Investigación en Hiperreactividad BronquialInstituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico, Distrito Federal, Mexico.Departamento de Biología Celular y FisiologíaInstituto de Investigaciones BiomédicasDepartamento de FarmacologíaFacultad de Medicina, Universidad Nacional Autónoma de México, Mexico, Distrito Federal 04510, MexicoDepartamento de Investigación en Hiperreactividad BronquialInstituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico, Distrito Federal, Mexico perusqui@unam.mx.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24781253

Citation

Montaño, Luis M., et al. "Androgens Are Bronchoactive Drugs That Act By Relaxing Airway Smooth Muscle and Preventing Bronchospasm." The Journal of Endocrinology, vol. 222, no. 1, 2014, pp. 1-13.
Montaño LM, Espinoza J, Flores-Soto E, et al. Androgens are bronchoactive drugs that act by relaxing airway smooth muscle and preventing bronchospasm. J Endocrinol. 2014;222(1):1-13.
Montaño, L. M., Espinoza, J., Flores-Soto, E., Chávez, J., & Perusquía, M. (2014). Androgens are bronchoactive drugs that act by relaxing airway smooth muscle and preventing bronchospasm. The Journal of Endocrinology, 222(1), 1-13. https://doi.org/10.1530/JOE-14-0074
Montaño LM, et al. Androgens Are Bronchoactive Drugs That Act By Relaxing Airway Smooth Muscle and Preventing Bronchospasm. J Endocrinol. 2014;222(1):1-13. PubMed PMID: 24781253.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Androgens are bronchoactive drugs that act by relaxing airway smooth muscle and preventing bronchospasm. AU - Montaño,Luis M, AU - Espinoza,Julia, AU - Flores-Soto,Edgar, AU - Chávez,Jaime, AU - Perusquía,Mercedes, Y1 - 2014/04/29/ PY - 2014/5/1/entrez PY - 2014/5/2/pubmed PY - 2014/10/1/medline KW - 5α-dihydrotestosterone KW - 5β-dihydrotestosterone KW - airway smooth muscle KW - asthma KW - bronchoactive steroids KW - testosterone SP - 1 EP - 13 JF - The Journal of endocrinology JO - J. Endocrinol. VL - 222 IS - 1 N2 - 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 (5α- and 5β-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. 5β-DHT was more potent for relaxing KCl-induced contraction, while TES and 5α-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(+) channels. These data indicate the absence of involvement of the epithelium-, NO- and K(+) 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(2+)]i increment. 5β-DHT was the most potent at decreasing KCl-induced [Ca(2+)]i increment and preventing bronchospasm. We suggest that androgen-induced brochorelaxation was mediated via decreased Ca(2+) influx through L-type Ca(2+)channels but additional Ca(2+) entry blockade may be involved. Molecular changes in androgen structure may determine its preferential site of action. SN - 1479-6805 UR - https://www.unboundmedicine.com/medline/citation/24781253/Androgens_are_bronchoactive_drugs_that_act_by_relaxing_airway_smooth_muscle_and_preventing_bronchospasm_ L2 - https://joe.bioscientifica.com/doi/10.1530/JOE-14-0074 DB - PRIME DP - Unbound Medicine ER -