PMC:7556165 / 11239-13124 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7556165","sourcedb":"PMC","sourceid":"7556165","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7556165","text":"A growing number of recent findings point to an important role of epigenetic mechanisms associated with several human diseases (Surguchov et al., 2017). In this context, several authors highlighted the regulatory role of 17β-estradiol (E2), a primary female sex steroid, in the expression of ACE2 in a tissue-dependent fashion. Liu et al. (2010) and Stelzig et al. (2020) found out that E2 downregulates ACE2 in kidney and differentiated airway epithelial cells, respectively. The latter result is particularly important, as the male-bias of ACE2 expression in the lung could account for the alleged higher susceptibility of males to COVID-19 symptoms following ACE2-dependent SARS-CoV-2 infection (section Links Between ACE2 and COVID-19) (Jin et al., 2020). Yet, Bukowska et al. (2017) observed that E2 increases ACE2 transcription and expression in human atrial tissue, while at the same time depressing the level of ACE protein. This mechanism attenuates the renin-angiotensin system and, in tandem with anti-inflammatory and anti-oxidative effects, enables a stronger response to myocardial stress and contributes to antiarhythmic effects. The upregulation of ACE2 (and downregulation of ACE) was clearly linked to binding of E2 to Estrogen Receptor alpha (ERα) (Bukowska et al., 2017). The E2-ERα complex might migrate to the nucleus to bind to estrogen response elements, although the actual mechanism is still obscure and should likely involve other co-factors to take into account the observed tissue bias of E2 regulation. Nonetheless, it was demonstrated that the Estrogen Related Receptor alpha (ERRα), which likewise ERα recognizes the estrogen response element in target genes, binds to ACE2 promoter to repress transcription (Tremblay et al., 2010; Lee et al., 2012). Hopefully, future studies will shed more light on the intriguing role of estrogens in ACE2 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