Sex steroids skew ACE2 expression in human airway: A contributing factor to sex differences in COVID-19?

Rama Satyanarayana Raju Kalidhindi, Niyati A. Borkar, Nilesh Sudhakar Ambhore, Christina M. Pabelick, Y. S. Prakash, Venkatachalem Sathish

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)L843-L847
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number5
StatePublished - Nov 3 2020


  • Airway smooth muscle
  • Estrogen
  • SARS-CoV-2
  • Sex difference
  • Testosterone

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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