Endocrine aspects of ACE2 regulation: RAAS, steroid hormones and SARS-CoV-2

in Journal of Endocrinology
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  • 1 M Young, Cardiovascular Endocrinology, Hudson Institute of Medical Research, Clayton, 3166, Australia
  • 2 C Clyne , Cancer Drug Discovery, Hudson Institute of Medical Research, Clayton, Australia
  • 3 K Chapman, Centre for Cardiovascular Science, The University of Edinburgh The Queen's Medical Research Institute, Edinburgh, EH16 4TJ, United Kingdom of Great Britain and Northern Ireland

Correspondence: Morag J Young, Email: morag.young@baker.edu.au

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 >5 million people worldwide. A key step in understanding the pathobiology of SARS-CoV-2 was identification of angiotensin converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 to gain entry into host cells. ACE2 is an establishsed component of the 'protective arm' of the renin-angiotensin-aldosterone-system (RAAS) and opposes ACE/angiotensin II (ANG II) pressor and tissue remodelling actions. Identification of ACE2 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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