Roles of steroid receptors in the lung and COVID-19

Abstract

COVID-19 symptoms and mortality are largely due to its devastating effects in the lungs. The disease is caused by the SARS (Severe Acute Respiratory Syndrome)-CoV-2 coronavirus, which requires host cell proteins such as ACE2 (angiotensin-converting enzyme 2) and TMPRSS2 (transmembrane serine protease 2) for infection of lung epithelia. The expression and function of the steroid hormone receptor family is important in many aspects that impact on COVID-19 effects in the lung – notably lung development and function, the immune system, and expression of TMPRSS2 and ACE2. This review provides a brief summary of current knowledge on the roles of the steroid hormone receptors [androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR), mineralocorticoid receptor (MR) and oestrogen receptor (ER)] in the lung, their effects on host cell proteins that facilitate SARS-CoV-2 uptake, and provides a snapshot of current clinical trials investigating the use of steroid receptor (SR) ligands to treat COVID-19.

The relationship between sex steroids (E2, progesterone, and AMH) levels and severity and fatality of COVID-19: A systematic review

“…The dissimilarities in vulnerability to viral infection in women and men seem to be reliant on sex hormone production in women [ 24 ]. Anti-androgens have the potential to treat the illness because all steroid receptors are expressed in the lung, and altering the activity of steroid receptors may be a key factor in mediating SARS-CoV-2 infections [ 25 ]. Additionally, a review finding implied that androgen was involved in the development and severity of COVID-19.…”

The Role of Cytochrome P450 Enzymes in COVID-19 Pathogenesis and Therapy

“…SARS studies show that 39.3% survivors had evidence of hypocortisolism 3 months after recovery, and the majority of the hypothalamic-pituitary-adrenal (HPA) axis dysfunction resolved within a year (Leow et al, 2005). In the current COVID-19 pandemic, as well as in the SARS-CoV and MERS epidemics, females have a substantially lower mortality rate than males, which can be explained by sex differences in the response to inflammation and sex steroid hormones (Al-Lami et al, 2020;Leach et al, 2021).…”

Glucocorticoids Immunotropic Effects Realization: the Role of Glucocorticoid Receptors, Transport and Regulatory Systems. The Literature Review

“…Описана регуляция экспрессии ГР интерфероном, так как 1А промоутер гена человеческого ГР содержит элемент, регулируемый интерфероном, который активирует его транскрипцию [40], а также подавление экспрессии ГР в лейкоцитах посредством повышения содержания фактора Gas5 при инфекционных процессах [41]. Обсуждается роль ГР в регуляции активности воспалительного процесса при COVID-19 [42]. Хроническое воспаление может приводить к дисфункции ГР за счет влияния цитокинов на белок-белковые взаимодействия [43].…”