Department of Medicine, Section of Endocrinology, Tulane University School of Medicine, New Orleans, LA, USA.
Tulane Center of Excellence in Sex-Based Biology & Medicine, New Orleans, LA, USA.
Endocrinology. 2021 Aug 1;162(8). doi: 10.1210/endocr/bqab114.
Coronavirus disease 2019 (COVID-19) is characterized by a gender disparity in severity, with men exhibiting higher hospitalization and mortality rates than women. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, infects cells following recognition and attachment of the viral spike glycoprotein to the angiotensin-converting enzyme 2 transmembrane protein, followed by spike protein cleavage and activation by cell surface transmembrane protease serine 2 (TMPRSS2). In prostate cancer cells, androgen acting on the androgen receptor increases TMPRSS2 expression, which has led to the hypothesis that androgen-dependent expression of TMPRSS2 in the lung may increase men's susceptibility to severe COVID-19 and that, accordingly, suppressing androgen production or action may mitigate COVID-19 severity by reducing SARS-CoV-2 amplification. Several ongoing clinical trials are testing the ability of androgen deprivation therapies or anti-androgens to mitigate COVID-19. This perspective discusses clinical and molecular advances on the rapidly evolving field of androgen receptor (AR) action on cell surface transmembrane protease serine 2 (TMPRSS2) expression and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the potential effect of anti-androgens on coronavirus disease 2019 (COVID-19) severity in male patients. It discusses limitations of current studies and offers insight for future directions.
新型冠状病毒病 2019（COVID-19）的严重程度存在性别差异，男性的住院和死亡率高于女性。导致 COVID-19 的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）在感染细胞之前，先识别并附着在血管紧张素转换酶 2 跨膜蛋白上，随后病毒刺突糖蛋白被细胞表面跨膜丝氨酸蛋白酶 2（TMPRSS2）切割和激活。在前列腺癌细胞中，雄激素作用于雄激素受体可增加 TMPRSS2 的表达，这导致了一种假设，即肺部雄激素依赖性表达的 TMPRSS2 可能会增加男性患严重 COVID-19 的易感性，因此，通过减少 SARS-CoV-2 的扩增来抑制雄激素的产生或作用可能会减轻 COVID-19 的严重程度。目前正在进行的几项临床试验正在测试雄激素剥夺疗法或抗雄激素药物减轻 COVID-19 的能力。本文从临床和分子角度探讨了雄激素受体（AR）对细胞表面跨膜丝氨酸蛋白酶 2（TMPRSS2）表达和严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染的快速发展领域的进展，以及抗雄激素对男性 COVID-19 严重程度的潜在影响。讨论了当前研究的局限性，并为未来的方向提供了思路。
