Androgens are effective bronchodilators with anti-inflammatory properties: A potential alternative for asthma therapy

Luis M. Montaño, Edgar Flores-Soto, Bettina Sommer, Héctor Solís-Chagoyán, Mercedes Perusquía

Resultado de la investigación: Contribución a una revistaArtículo de revisión

Resumen

Changes in plasma androgen levels in asthmatic men may be linked to asthma severity, seemingly acting through nongenomic and genomic effects. Nongenomic effects include rapid relaxation of carbachol or antigenic challenge pre-contracted guinea pig airway smooth muscle (ASM) in vitro: testosterone (TES) blocks L-type voltage dependent Ca2+ channels, stored operated Ca2+ channels, inositol 1,4,5-trisphosphate receptors and promotes prostaglandin E2 biosynthesis. In ASM at rest, TES lowers basal intracellular Ca2+ concentration and tension, maintaining a proper airway patency keeping steady smooth muscle tension and basal intracellular Ca2+ concentration at rest. Moreover, the bronchospasm in sensitized guinea-pigs was ablated by dehydroepiandrosterone (DHEA), a precursor of steroids, TES and its metabolites 5α- and 5β-dihydrotestosterone (DHT). On the other hand, genomic effects related to androgens' anti-inflammatory properties in asthma have been recently studied. Briefly, TES negatively regulates type 2 immune response sustained by CD4+ Th2 and group 2 innate lymphoid cells, diminishing allergic airway inflammation in males. Also, novel findings establish that TES decreases interleukin (IL)-17A protein expression produced by CD4+ Th17 cells and therefore neutrophilic airway inflammation. Clearly, DHEA, TES or its 5β-reduced metabolite that possesses minimal androgenic effect, might have potential therapeutic capacities in the treatment of severe asthma via mechanisms distinct from corticosteroid treatment.

Idioma originalInglés
Número de artículo108509
PublicaciónSteroids
Volumen153
DOI
EstadoPublicada - ene 2020

Huella dactilar

Bronchodilator Agents
Complementary Therapies
Androgens
Testosterone
Anti-Inflammatory Agents
Asthma
Smooth Muscle
Muscle
Dehydroepiandrosterone
Metabolites
Guinea Pigs
Inflammation
Inositol 1,4,5-Trisphosphate Receptors
Th17 Cells
Bronchial Spasm
Muscle Tonus
Interleukin-17
Dihydrotestosterone
Biosynthesis
Carbachol

Citar esto

Montaño, Luis M. ; Flores-Soto, Edgar ; Sommer, Bettina ; Solís-Chagoyán, Héctor ; Perusquía, Mercedes. / Androgens are effective bronchodilators with anti-inflammatory properties : A potential alternative for asthma therapy. En: Steroids. 2020 ; Vol. 153.
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abstract = "Changes in plasma androgen levels in asthmatic men may be linked to asthma severity, seemingly acting through nongenomic and genomic effects. Nongenomic effects include rapid relaxation of carbachol or antigenic challenge pre-contracted guinea pig airway smooth muscle (ASM) in vitro: testosterone (TES) blocks L-type voltage dependent Ca2+ channels, stored operated Ca2+ channels, inositol 1,4,5-trisphosphate receptors and promotes prostaglandin E2 biosynthesis. In ASM at rest, TES lowers basal intracellular Ca2+ concentration and tension, maintaining a proper airway patency keeping steady smooth muscle tension and basal intracellular Ca2+ concentration at rest. Moreover, the bronchospasm in sensitized guinea-pigs was ablated by dehydroepiandrosterone (DHEA), a precursor of steroids, TES and its metabolites 5α- and 5β-dihydrotestosterone (DHT). On the other hand, genomic effects related to androgens' anti-inflammatory properties in asthma have been recently studied. Briefly, TES negatively regulates type 2 immune response sustained by CD4+ Th2 and group 2 innate lymphoid cells, diminishing allergic airway inflammation in males. Also, novel findings establish that TES decreases interleukin (IL)-17A protein expression produced by CD4+ Th17 cells and therefore neutrophilic airway inflammation. Clearly, DHEA, TES or its 5β-reduced metabolite that possesses minimal androgenic effect, might have potential therapeutic capacities in the treatment of severe asthma via mechanisms distinct from corticosteroid treatment.",
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Androgens are effective bronchodilators with anti-inflammatory properties : A potential alternative for asthma therapy. / Montaño, Luis M.; Flores-Soto, Edgar; Sommer, Bettina; Solís-Chagoyán, Héctor; Perusquía, Mercedes.

En: Steroids, Vol. 153, 108509, 01.2020.

Resultado de la investigación: Contribución a una revistaArtículo de revisión

TY - JOUR

T1 - Androgens are effective bronchodilators with anti-inflammatory properties

T2 - A potential alternative for asthma therapy

AU - Montaño, Luis M.

AU - Flores-Soto, Edgar

AU - Sommer, Bettina

AU - Solís-Chagoyán, Héctor

AU - Perusquía, Mercedes

PY - 2020/1

Y1 - 2020/1

N2 - Changes in plasma androgen levels in asthmatic men may be linked to asthma severity, seemingly acting through nongenomic and genomic effects. Nongenomic effects include rapid relaxation of carbachol or antigenic challenge pre-contracted guinea pig airway smooth muscle (ASM) in vitro: testosterone (TES) blocks L-type voltage dependent Ca2+ channels, stored operated Ca2+ channels, inositol 1,4,5-trisphosphate receptors and promotes prostaglandin E2 biosynthesis. In ASM at rest, TES lowers basal intracellular Ca2+ concentration and tension, maintaining a proper airway patency keeping steady smooth muscle tension and basal intracellular Ca2+ concentration at rest. Moreover, the bronchospasm in sensitized guinea-pigs was ablated by dehydroepiandrosterone (DHEA), a precursor of steroids, TES and its metabolites 5α- and 5β-dihydrotestosterone (DHT). On the other hand, genomic effects related to androgens' anti-inflammatory properties in asthma have been recently studied. Briefly, TES negatively regulates type 2 immune response sustained by CD4+ Th2 and group 2 innate lymphoid cells, diminishing allergic airway inflammation in males. Also, novel findings establish that TES decreases interleukin (IL)-17A protein expression produced by CD4+ Th17 cells and therefore neutrophilic airway inflammation. Clearly, DHEA, TES or its 5β-reduced metabolite that possesses minimal androgenic effect, might have potential therapeutic capacities in the treatment of severe asthma via mechanisms distinct from corticosteroid treatment.

AB - Changes in plasma androgen levels in asthmatic men may be linked to asthma severity, seemingly acting through nongenomic and genomic effects. Nongenomic effects include rapid relaxation of carbachol or antigenic challenge pre-contracted guinea pig airway smooth muscle (ASM) in vitro: testosterone (TES) blocks L-type voltage dependent Ca2+ channels, stored operated Ca2+ channels, inositol 1,4,5-trisphosphate receptors and promotes prostaglandin E2 biosynthesis. In ASM at rest, TES lowers basal intracellular Ca2+ concentration and tension, maintaining a proper airway patency keeping steady smooth muscle tension and basal intracellular Ca2+ concentration at rest. Moreover, the bronchospasm in sensitized guinea-pigs was ablated by dehydroepiandrosterone (DHEA), a precursor of steroids, TES and its metabolites 5α- and 5β-dihydrotestosterone (DHT). On the other hand, genomic effects related to androgens' anti-inflammatory properties in asthma have been recently studied. Briefly, TES negatively regulates type 2 immune response sustained by CD4+ Th2 and group 2 innate lymphoid cells, diminishing allergic airway inflammation in males. Also, novel findings establish that TES decreases interleukin (IL)-17A protein expression produced by CD4+ Th17 cells and therefore neutrophilic airway inflammation. Clearly, DHEA, TES or its 5β-reduced metabolite that possesses minimal androgenic effect, might have potential therapeutic capacities in the treatment of severe asthma via mechanisms distinct from corticosteroid treatment.

KW - Androgens

KW - Anti-inflammatory

KW - Asthma therapy

KW - Bronchodilatation

KW - Genomic and nongenomic actions

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JO - Steroids

JF - Steroids

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