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Endocrine aspects of ACE2 regulation: RAAS, steroid hormones and SARS-CoV-2.
J Endocrinol. 2020 Nov; 247(2):R45-R62.JE

Abstract

Coronavirus disease (COVID-19) is caused by a new strain of coronavirus, the severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2. At the time of writing, SARS-CoV-2 has infected over 5 million people worldwide. A key step in understanding the pathobiology of the SARS-CoV-2 was the identification of -converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 to gain entry into host cells. ACE2 is an established component of the 'protective arm' of the renin-angiotensin-aldosterone-system (RAAS) that opposes ACE/angiotensin II (ANG II) pressor and tissue remodelling actions. Identification of ACE2 as the entry point for SARS-CoV-2 into cells quickly focused attention on the use of ACE inhibitors (ACEi), angiotensin receptor blockers (ARB) and mineralocorticoid receptor antagonists (MRA) in patients with hypertension and cardiovascular disease given that these pharmacological agents upregulate ACE2 expression in target cells. ACE2 is cleaved from the cells by metalloproteases ADAM10 and ADAM17. Steroid hormone receptors regulate multiple components of the RAAS and may contribute to the observed variation in the incidence of severe COVID-19 between men and women, and in patients with pre-existing endocrine-related disease. Moreover, glucocorticoids play a critical role in the acute and chronic management of inflammatory disease, independent of any effect on RAAS activity. Dexamethasone, a synthetic glucocorticoid, has emerged as a life-saving treatment in severe COVID-19. This review will examine the endocrine mechanisms that control ACE2 and discusses the impact of therapies targeting the RAAS, glucocorticoid and other endocrine systems for their relevance to the impact of SARS-CoV-2 infection and the treatment and recovery from COVID-19-related critical illness.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Young MJ
Baker Heart and Diabetes Institute, Prahran, Australia. Hudson Institute of Medical Research, Clayton, Australia.
Clyne CD
Hudson Institute of Medical Research, Clayton, Australia.
Chapman KE
The University/BHF Centre for Cardiovascular Science, The University of Edinburgh, The Queen's Medical Research Institute, Edinburgh, UK.

MeSH

AldosteroneAngiotensin-Converting Enzyme 2Angiotensin-Converting Enzyme InhibitorsAnimalsBetacoronavirusCOVID-19Coronavirus InfectionsHumansPandemicsPeptidyl-Dipeptidase APneumonia, ViralReceptors, SteroidRenin-Angiotensin SystemSARS-CoV-2Steroids

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

32966970

Citation

Young, Morag J., et al. "Endocrine Aspects of ACE2 Regulation: RAAS, Steroid Hormones and SARS-CoV-2." The Journal of Endocrinology, vol. 247, no. 2, 2020, pp. R45-R62.
Young MJ, Clyne CD, Chapman KE. Endocrine aspects of ACE2 regulation: RAAS, steroid hormones and SARS-CoV-2. J Endocrinol. 2020;247(2):R45-R62.
Young, M. J., Clyne, C. D., & Chapman, K. E. (2020). Endocrine aspects of ACE2 regulation: RAAS, steroid hormones and SARS-CoV-2. The Journal of Endocrinology, 247(2), R45-R62. https://doi.org/10.1530/JOE-20-0260
Young MJ, Clyne CD, Chapman KE. Endocrine Aspects of ACE2 Regulation: RAAS, Steroid Hormones and SARS-CoV-2. J Endocrinol. 2020;247(2):R45-R62. PubMed PMID: 32966970.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endocrine aspects of ACE2 regulation: RAAS, steroid hormones and SARS-CoV-2. AU - Young,Morag J, AU - Clyne,Colin D, AU - Chapman,Karen E, PY - 2020/7/6/received PY - 2020/8/5/accepted PY - 2020/9/23/entrez PY - 2020/9/24/pubmed PY - 2020/10/2/medline KW - ACE2 KW - COVID-19 KW - SARS-CoV-2 KW - angiotensin KW - corticosteroid KW - dexamethasone KW - glucocorticoid receptor KW - nuclear receptor SP - R45 EP - R62 JF - The Journal of endocrinology JO - J Endocrinol VL - 247 IS - 2 N2 - Coronavirus disease (COVID-19) is caused by a new strain of coronavirus, the severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2. At the time of writing, SARS-CoV-2 has infected over 5 million people worldwide. A key step in understanding the pathobiology of the SARS-CoV-2 was the identification of -converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 to gain entry into host cells. ACE2 is an established component of the 'protective arm' of the renin-angiotensin-aldosterone-system (RAAS) that opposes ACE/angiotensin II (ANG II) pressor and tissue remodelling actions. Identification of ACE2 as the entry point for SARS-CoV-2 into cells quickly focused attention on the use of ACE inhibitors (ACEi), angiotensin receptor blockers (ARB) and mineralocorticoid receptor antagonists (MRA) in patients with hypertension and cardiovascular disease given that these pharmacological agents upregulate ACE2 expression in target cells. ACE2 is cleaved from the cells by metalloproteases ADAM10 and ADAM17. Steroid hormone receptors regulate multiple components of the RAAS and may contribute to the observed variation in the incidence of severe COVID-19 between men and women, and in patients with pre-existing endocrine-related disease. Moreover, glucocorticoids play a critical role in the acute and chronic management of inflammatory disease, independent of any effect on RAAS activity. Dexamethasone, a synthetic glucocorticoid, has emerged as a life-saving treatment in severe COVID-19. This review will examine the endocrine mechanisms that control ACE2 and discusses the impact of therapies targeting the RAAS, glucocorticoid and other endocrine systems for their relevance to the impact of SARS-CoV-2 infection and the treatment and recovery from COVID-19-related critical illness. SN - 1479-6805 UR - https://www.unboundmedicine.com/medline/citation/32966970/Endocrine_aspects_of_ACE2_regulation:_RAAS_steroid_hormones_and_SARS_CoV_2_ DB - PRIME DP - Unbound Medicine ER -