Oestrogen Synthesis, Oestrogen Metabolism and Functional Oestrogen Receptors in Bovine Aortic Endothelial Cells

Bayard, Françis; Clamens, Simone; Delsol, Georges; Blaes, Nelly; Maret, Arlette; Faye, Jean-Charles

doi:10.1002/9780470514757.ch7

Cited by 28 publications

(9 citation statements)

References 46 publications

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“…To test the hypothesis that estrogen is involved in the protection of endothelial cells from IL-6-induced oxidative stress, BAECs were treated with various doses of 17β-estradiol (10 nmol/L to 10 μmol/L, 24 hrs) following IL-6 exposure (100 ng/mL, 30 min). Of note, estrogen receptors, ERα and ERβ, have been previously described to be functional in BAECs [ 52 , 53 ]. At a minimal dose of 10 nmol/L, 17β-estradiol almost completely abrogated IL-6-induced upregulation of NOX2 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Therapeutic application of estrogen for COVID-19: Attenuation of SARS-CoV-2 spike protein and IL-6 stimulated, ACE2-dependent NOX2 activation, ROS production and MCP-1 upregulation in endothelial cells

Youn

Zhang

et al. 2021

Redox Biology

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The outbreak of COVID-19 has remained uncontained with urgent need for robust therapeutics. Males are more susceptible than females, and more often to develop into severe cases with higher mortality. This predisposition is potentially linked to higher prevalence of cigarette smoking. Nonetheless, we found for the first time that cigarette smoking extract (CSE) had no effect on angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) expression in endothelial cells. The otherwise observed worse outcomes in smokers is likely linked to baseline respiratory diseases associated with chronic smoking. Instead, we hypothesized that estrogen mediated protection might underlie less severe disease in females. Of note, endothelial inflammation and barrier dysfunction are major mediators of disease progression, and development of acute respiratory distress syndrome (ARDS) and multi-organ failure in patients with COVID-19. Therefore, we investigated the protective effects of estrogen on endothelial cells against oxidative stress induced by interleukin-6 (IL-6) and SARS-CoV-2 spike protein (S protein). Indeed, 17β-estradiol completely reversed IL-6 and S protein-induced selective activation of NADPH oxidase isoform 2 (NOX2), reactive oxygen species (ROS) production, ACE2 upregulation and induction of pro-inflammatory gene monocyte chemoattractant protein-1 (MCP-1) in endothelial cells to effectively attenuate endothelial cell dysfunction. Of note, co-treatment with CSE had no additional effects on S protein stimulated endothelial oxidative stress, again indicating that current smoking status is likely unrelated to more severe disease in chronic smokers. These data indicate that estrogen may serve as a novel therapy for patients with COVID-19 via inhibition of initial viral responses and attenuation of cytokine storm induced endothelial dysfunction, to substantially alleviate severity of the disease and mortality, especially in men. Short-term application of estrogen may therefore be readily used in the clinical management of COVID-19 as a robust therapeutic option.

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Section: Resultsmentioning

confidence: 99%

Therapeutic application of estrogen for COVID-19: Attenuation of SARS-CoV-2 spike protein and IL-6 stimulated, ACE2-dependent NOX2 activation, ROS production and MCP-1 upregulation in endothelial cells

Youn

Zhang

et al. 2021

Redox Biology

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“…Aromatase activity has been confirmed in female rat arterial smooth muscle cells (SMCs) and in bovine coronary endothelial cells (ECs) in vitro [ 96 , 97 ]. Harada et al further demonstrated aromatase activity in human male and female arterial SMCs, but not in female ECs, which could potentially indicate autocrine/paracrine E2 activity [ 89 ].…”

Section: Aromatase and The Cardiovascular Systemmentioning

confidence: 99%

The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy

et al. 2017

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Epidemiologic studies have previously suggested that premenopausal females have reduced incidence of cardiovascular disease (CVD) when compared to age-matched males, and the incidence and severity of CVD increases postmenopause. The lower incidence of cardiovascular disease in women during reproductive age is attributed at least in part to estrogen (E2). E2 binds to the traditional E2 receptors (ERs), estrogen receptor alpha (ERα), and estrogen receptor beta (ERβ), as well as the more recently identified G-protein-coupled ER (GPR30), and can exert both genomic and non-genomic actions. This review summarizes the protective role of E2 and its receptors in the cardiovascular system and discusses its underlying mechanisms with an emphasis on oxidative stress, fibrosis, angiogenesis, and vascular function. This review also presents the sexual dimorphic role of ERs in modulating E2 action in cardiovascular disease. The controversies surrounding the clinical use of exogenous E2 as a therapeutic agent for cardiovascular disease in women due to the possible risks of thrombotic events, cancers, and arrhythmia are also discussed. Endogenous local E2 biosynthesis from the conversion of testosterone to E2 via aromatase enzyme offers a novel therapeutic paradigm. Targeting specific ERs in the cardiovascular system may result in novel and possibly safer therapeutic options for cardiovascular protection.

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“…Extragonadal estrogens are synthesized in different organs or tissues, such as bone [Bruch et al, 1992;Bayard et al, 1995], adipose tissue [Simpson et al, 1981], vascular endothelial and aortic smooth muscle cells [Sasano et al, 1999], and several sites in the brain [Naftolin et al, 1975].…”

Section: Discussionmentioning

confidence: 99%

Pituitary Aromatase P450 May Be Involved in Maintenance of the Population of Luteinizing Hormone-Positive Pituitary Cells in Mice

Carretero¹,

López

Catalano-Iniesta³

et al. 2016

Cells Tissues Organs

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As aromatase P450 is located in several pituitary cells, testosterone can be transformed into 17β-estradiol in the gland by the enzyme. The possible role of this transformation in pituitary function remains to be elucidated, but some evidence suggests a physiological and pathophysiological role for pituitary aromatase. To determine its relevance in the modulation of pituitary function, mainly associated with reproduction, luteinizing hormone (LH)-positive cells in the hypophysis of female and male aromatase knockout (ArKO) mice were studied. In all LH-positive cells, significant increases in the cellular (p < 0.01) and nuclear (p < 0.05) areas were found in the ArKO mice compared to the wild-type mice. In the ArKO mice, LH-positive cells were more abundant (p < 0.01); they were characterized by a stronger cytoplasmic reaction and the cells were more polygonal and exhibited more short, thick cytoplasmic prolongations than those in the wild-type mice. Moreover, LH-positive cells showed a greater proliferation rate in the ArKO mice compared to the wild-type mice (p < 0.01). These findings suggest that the local production of estradiol mediated by pituitary aromatase is necessary for the regulation of LH-positive gonadotropic cells, exerting an autoparacrine inhibitory regulation. These results could underlie the higher pituitary aromatase expression observed in male versus female mice. Similar effects were found in ArKO male and female mice, suggesting that in both sexes the effects of estrogens on maintenance of the LH-positive pituitary cell population could be related to the local aromatization of testosterone to estradiol inside the hypophysis. Therefore, aromatase could modulate pituitary LH-positive cells in males through local estradiol synthesis.

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Oestrogen Synthesis, Oestrogen Metabolism and Functional Oestrogen Receptors in Bovine Aortic Endothelial Cells

Cited by 28 publications

References 46 publications

Therapeutic application of estrogen for COVID-19: Attenuation of SARS-CoV-2 spike protein and IL-6 stimulated, ACE2-dependent NOX2 activation, ROS production and MCP-1 upregulation in endothelial cells

Therapeutic application of estrogen for COVID-19: Attenuation of SARS-CoV-2 spike protein and IL-6 stimulated, ACE2-dependent NOX2 activation, ROS production and MCP-1 upregulation in endothelial cells

The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy

Pituitary Aromatase P450 May Be Involved in Maintenance of the Population of Luteinizing Hormone-Positive Pituitary Cells in Mice

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