tetano
Editor, Senior Moderator
Am J Physiol Lung Cell Mol Physiol
. 2020 Sep 30.
doi: 10.1152/ajplung.00391.2020. Online ahead of print.
Sex steroids skew ACE2 expression in human airway: A contributing factor to sex differences in COVID-19?
Rama Satyanarayana Raju Kalidhindi[SUP] 1 [/SUP], Niyati A Borkar[SUP] 1 [/SUP], Nilesh Sudhakar Ambhore[SUP] 1 [/SUP], Christina M Pabelick[SUP] 2 [/SUP], Y S Prakash[SUP] 3 [/SUP], Venkatachalem Sathish[SUP] 1 [/SUP]
Affiliations
Abstract
The incidence, severity and mortality of ongoing coronavirus infectious disease-19 (COVID-19) is greater in men compared to women, but the underlying factors contributing to this sex difference are still being explored. In the current study, using primary isolated human airway smooth muscle (ASM) cells from normal males vs. females as a model, we explored the effect of estrogen vs. testosterone in modulating the expression of angiotensin converting enzyme 2 (ACE2), a cell entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using confocal imaging, we found that ACE2 is expressed in human ASM. Furthermore, Western analysis of ASM cell lysates showed significantly lower ACE2 expression in females compared to males at baseline. In addition, ASM cells exposed to estrogen and testosterone for 24 h showed that testosterone significantly upregulates ACE2 expression in both males and females, whereas estrogen downregulates ACE2, albeit not significant compared to vehicle. These intrinsic and sex steroids induced differences may help explain sex differences in COVID-19.
Keywords: Airway smooth muscle; Estrogen; SARS-CoV-2; Sex difference; Testosterone
. 2020 Sep 30.
doi: 10.1152/ajplung.00391.2020. Online ahead of print.
Sex steroids skew ACE2 expression in human airway: A contributing factor to sex differences in COVID-19?
Rama Satyanarayana Raju Kalidhindi[SUP] 1 [/SUP], Niyati A Borkar[SUP] 1 [/SUP], Nilesh Sudhakar Ambhore[SUP] 1 [/SUP], Christina M Pabelick[SUP] 2 [/SUP], Y S Prakash[SUP] 3 [/SUP], Venkatachalem Sathish[SUP] 1 [/SUP]
Affiliations
- PMID: 32996784
- DOI: 10.1152/ajplung.00391.2020
Abstract
The incidence, severity and mortality of ongoing coronavirus infectious disease-19 (COVID-19) is greater in men compared to women, but the underlying factors contributing to this sex difference are still being explored. In the current study, using primary isolated human airway smooth muscle (ASM) cells from normal males vs. females as a model, we explored the effect of estrogen vs. testosterone in modulating the expression of angiotensin converting enzyme 2 (ACE2), a cell entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using confocal imaging, we found that ACE2 is expressed in human ASM. Furthermore, Western analysis of ASM cell lysates showed significantly lower ACE2 expression in females compared to males at baseline. In addition, ASM cells exposed to estrogen and testosterone for 24 h showed that testosterone significantly upregulates ACE2 expression in both males and females, whereas estrogen downregulates ACE2, albeit not significant compared to vehicle. These intrinsic and sex steroids induced differences may help explain sex differences in COVID-19.
Keywords: Airway smooth muscle; Estrogen; SARS-CoV-2; Sex difference; Testosterone