Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes

Abstract 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 seve...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mehdi Baratchian, Jeffrey M. McManus, Mike P. Berk, Fumihiko Nakamura, Sanjay Mukhopadhyay, Weiling Xu, Serpil Erzurum, Judy Drazba, John Peterson, Eric A. Klein, Benjamin Gaston, Nima Sharifi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6ebf2e7f44a9410abac21588fc2e74c2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6ebf2e7f44a9410abac21588fc2e74c2
record_format	dspace
spelling	oai:doaj.org-article:6ebf2e7f44a9410abac21588fc2e74c22021-12-02T15:49:35ZAndrogen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes10.1038/s41598-021-90491-12045-2322https://doaj.org/article/6ebf2e7f44a9410abac21588fc2e74c22021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90491-1https://doaj.org/toc/2045-2322Abstract 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 administration. 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.Mehdi BaratchianJeffrey M. McManusMike P. BerkFumihiko NakamuraSanjay MukhopadhyayWeiling XuSerpil ErzurumJudy DrazbaJohn PetersonEric A. KleinBenjamin GastonNima SharifiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mehdi Baratchian Jeffrey M. McManus Mike P. Berk Fumihiko Nakamura Sanjay Mukhopadhyay Weiling Xu Serpil Erzurum Judy Drazba John Peterson Eric A. Klein Benjamin Gaston Nima Sharifi Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes
description	Abstract 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 administration. 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.
format	article
author	Mehdi Baratchian Jeffrey M. McManus Mike P. Berk Fumihiko Nakamura Sanjay Mukhopadhyay Weiling Xu Serpil Erzurum Judy Drazba John Peterson Eric A. Klein Benjamin Gaston Nima Sharifi
author_facet	Mehdi Baratchian Jeffrey M. McManus Mike P. Berk Fumihiko Nakamura Sanjay Mukhopadhyay Weiling Xu Serpil Erzurum Judy Drazba John Peterson Eric A. Klein Benjamin Gaston Nima Sharifi
author_sort	Mehdi Baratchian
title	Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes
title_short	Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes
title_full	Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes
title_fullStr	Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes
title_full_unstemmed	Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes
title_sort	androgen regulation of pulmonary ar, tmprss2 and ace2 with implications for sex-discordant covid-19 outcomes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6ebf2e7f44a9410abac21588fc2e74c2
work_keys_str_mv	AT mehdibaratchian androgenregulationofpulmonaryartmprss2andace2withimplicationsforsexdiscordantcovid19outcomes AT jeffreymmcmanus androgenregulationofpulmonaryartmprss2andace2withimplicationsforsexdiscordantcovid19outcomes AT mikepberk androgenregulationofpulmonaryartmprss2andace2withimplicationsforsexdiscordantcovid19outcomes AT fumihikonakamura androgenregulationofpulmonaryartmprss2andace2withimplicationsforsexdiscordantcovid19outcomes AT sanjaymukhopadhyay androgenregulationofpulmonaryartmprss2andace2withimplicationsforsexdiscordantcovid19outcomes AT weilingxu androgenregulationofpulmonaryartmprss2andace2withimplicationsforsexdiscordantcovid19outcomes AT serpilerzurum androgenregulationofpulmonaryartmprss2andace2withimplicationsforsexdiscordantcovid19outcomes AT judydrazba androgenregulationofpulmonaryartmprss2andace2withimplicationsforsexdiscordantcovid19outcomes AT johnpeterson androgenregulationofpulmonaryartmprss2andace2withimplicationsforsexdiscordantcovid19outcomes AT ericaklein androgenregulationofpulmonaryartmprss2andace2withimplicationsforsexdiscordantcovid19outcomes AT benjamingaston androgenregulationofpulmonaryartmprss2andace2withimplicationsforsexdiscordantcovid19outcomes AT nimasharifi androgenregulationofpulmonaryartmprss2andace2withimplicationsforsexdiscordantcovid19outcomes
_version_	1718385695753502720

Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes

Ejemplares similares