Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. Montesano 49, I-80131 Naples, Italy.
Department of Pharmacy (DIFARMA), University of Salerno, Via Giovanni Paolo II 132 Fisciano, I-84084 Salerno, Italy.
Pharmacol Res. 2020 Aug;158:104905. doi: 10.1016/j.phrs.2020.104905. Epub 2020 May 19.
Androgen levels inversely correlate with the incidence, susceptibility and severity of asthma. However, whether male sex hormones such as 5α-dihydrotestosterone (DHT) have beneficial effects on asthma symptoms and/or could affect asthma susceptibility have not been investigated. DHT administration to female mice, during the sensitization phase, abrogates the sex bias in bronchial hyperreactivity. This effect correlates with inhibition of leukotriene biosynthesis in the lung. DHT significantly inhibits also other asthma-like features such as airway hyperplasia and mucus production in sensitized female mice. Conversely, DHT does not affect plasma IgE levels as well as CD3CD4 IL-4 cell and IgEc-Kit cell infiltration within the lung but prevents pulmonary mast cell activation. The in vitro study on RBL-2H3 cells confirms that DHT inhibits mast cell degranulation. In conclusion, our data demonstrate that immunomodulatory effects of DHT on mast cell activation prevent the translation of allergen sensitization into clinical manifestation of asthma.
雄激素水平与哮喘的发病率、易感性和严重程度呈负相关。然而，男性性激素如 5α-二氢睾酮（DHT）是否对哮喘症状有有益影响，或者是否会影响哮喘易感性，尚未得到研究。在致敏阶段向雌性小鼠给予 DHT，可消除支气管高反应性的性别偏向。这种作用与肺内白三烯生物合成的抑制相关。DHT 还显著抑制其他类似哮喘的特征，如致敏雌性小鼠的气道增生和黏液产生。相反，DHT 不影响血浆 IgE 水平以及肺内的 CD3CD4IL-4 细胞和 IgEc-Kit 细胞浸润，但可防止肺肥大细胞活化。在 RBL-2H3 细胞上的体外研究证实，DHT 抑制肥大细胞脱颗粒。总之，我们的数据表明，DHT 对肥大细胞活化的免疫调节作用可防止过敏原致敏转化为哮喘的临床表现。
