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

Autor: Kalidhindi RSR; Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, North Dakota., Borkar NA; Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, North Dakota., Ambhore NS; Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, North Dakota., Pabelick CM; Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota.; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota., Prakash YS; Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota.; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota., Sathish V; Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, North Dakota.
Jazyk: angličtina
Zdroj: American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2020 Nov 01; Vol. 319 (5), pp. L843-L847. Date of Electronic Publication: 2020 Sep 30.
DOI: 10.1152/ajplung.00391.2020
Abstrakt: 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.
Databáze: MEDLINE