TY - JOUR
T1 - Sex steroids skew ACE2 expression in human airway
T2 - A contributing factor to sex differences in COVID-19?
AU - Kalidhindi, Rama Satyanarayana Raju
AU - Borkar, Niyati A.
AU - Ambhore, Nilesh Sudhakar
AU - Pabelick, Christina M.
AU - Prakash, Y. S.
AU - Sathish, Venkatachalem
N1 - Publisher Copyright:
Copyright © 2020 the American Physiological Society
PY - 2020/11/3
Y1 - 2020/11/3
N2 - The incidence, severity, and mortality of ongoing coronavirus infectious disease 19 (COVID-19) is greater in men compared with 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 versus females as a model, we explored the effect of estrogen versus 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 with 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 with vehicle. These intrinsic and sex steroids induced differences may help explain sex differences in COVID-19.
AB - The incidence, severity, and mortality of ongoing coronavirus infectious disease 19 (COVID-19) is greater in men compared with 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 versus females as a model, we explored the effect of estrogen versus 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 with 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 with vehicle. These intrinsic and sex steroids induced differences may help explain sex differences in COVID-19.
KW - Airway smooth muscle
KW - Estrogen
KW - SARS-CoV-2
KW - Sex difference
KW - Testosterone
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U2 - 10.1152/AJPLUNG.00391.2020
DO - 10.1152/AJPLUNG.00391.2020
M3 - Article
C2 - 32996784
AN - SCOPUS:85095673974
SN - 1040-0605
VL - 319
SP - L843-L847
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 5
ER -