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

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.