Sex, androgens and regulation of pulmonary AR, TMPRSS2 and ACE2
| Autor: | John W. Peterson, Mehdi Baratchian, Fumihiko Nakamura, Serpil C. Erzurum, M. Berk, Nima Sharifi, Sanjay Mukhopadhyay, Gaston Ben, Jeffrey M. McManus, Eric A. Klein, Weiling Xu, Judy Drazba |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Coronavirus disease 2019 (COVID-19) Physiology Male mice Angiogenesis Inhibitors urologic and male genital diseases TMPRSS2 Article chemistry.chemical_compound Mice Cell Line Tumor Nitriles Phenylthiohydantoin Androgen Receptor Antagonists Enzalutamide Androgen receptor antagonist Medicine Animals Humans Lung Steroid hormones Prostate cancer Smokers business.industry Serine Endopeptidases COVID-19 Immunohistochemistry Sexual dimorphism Clinical trial chemistry Gene Expression Regulation Receptors Androgen Benzamides Androgens Chromatin Immunoprecipitation Sequencing Female Angiotensin-Converting Enzyme 2 business hormones hormone substitutes and hormone antagonists |
| Zdroj: | bioRxiv article-version (status) pre article-version (number) 2 Scientific Reports |
| Popis: | The sex discordance in COVID-19 outcomes has been widely recognized, with males generally faring worse than females and a potential link to sex steroids. A plausible mechanism is androgen-induced expression of TMPRSS2 and/or ACE2 in pulmonary tissues that may increase susceptibility or severity in males. This hypothesis is the subject of several clinical trials of anti-androgen therapies around the world. Here, we investigated the sex-associated TMPRSS2 and ACE2 expression in human and mouse lungs and interrogated the possibility of pharmacologic modification of their expression with anti-androgens. We found no evidence for increased TMPRSS2 expression in the lungs of males compared to females in humans or mice. Furthermore, in male mice, treatment with the androgen receptor antagonist enzalutamide did not decrease pulmonary TMPRSS2. On the other hand, ACE2 and AR expression was sexually dimorphic and higher in males than females. ACE2 was moderately suppressible with enzalutamide therapy. Our work suggests that sex differences in COVID-19 outcomes attributable to viral entry are independent of TMPRSS2. Modest changes in ACE2 could account for some of the sex discordance. |
| Databáze: | OpenAIRE |
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