scholarly journals Structural insights into decreased affinity of SARS-CoV-2 to ACE2 by steroids

2020 ◽  
Author(s):  
Alireza Mansouri ◽  
Rasoul Kowsar ◽  
Khaled Sadeghi ◽  
Akio Miyamoto
Keyword(s):  
Steroid Hormones ◽  
Binding Free Energy ◽  
Sex Steroid Hormones ◽  
Spike Protein ◽  
Sex Steroid ◽  
Sex Steroid Hormone ◽  
Risk Of Death ◽  
Main Protease ◽  
Anti Inflammatory ◽  
Novel Coronavirus

Abstract The novel coronavirus disease (COVID-19) presently poses significant concerns around the world. Latest reports show that the degree of disease and mortality of COVID-19 infected patients may vary from gender to gender with a very high risk of death for seniors. Clearly, different levels of sex steroid hormones are found in both men and women. It was hypothesized that sex steroid hormones estradiol (E2), progesterone (P4), and testosterone (T) may change the interaction of coronavirus spike protein with angiotensin converting enzyme-2 (ACE2, which is the major SARS-CoV-2 cell entry receptor.) in the presence or absence of dexamethasone (DEX, the potential anti-inflammatory agents). Data showed that E2 was more strongly to interact with the main protease of the coronavirus, while T had the lowest affinity for coronavirus spike protein than E2 and P4. The binding energy of the spike protein to ACE2 was increased in the presence of five molecules of each steroid; the greatest increase was observed by DEX and E2. The binding free energy of the spike protein to ACE2 was the highest in the presence of both E2 and DEX molecules. Together, the interaction between spike protein and ACE2 can be disrupted by female sex steroid hormone E2 and to a greater extent by E2 and anti-inflammatory DEX, in part explaining the lower incidence of COVID-19 infection in women than men. The potential use of E2 and DEX to reduce coronavirus attachment to ACE2 in the early phase of the coronavirus invasion needs to be clinically investigated.

scholarly journals Computational Modeling Indicates A Decreased Affinity of SARS-CoV-2 to ACE2 by Steroids

2020 ◽  
Author(s):  
Alireza Mansouri ◽  
Rasoul Kowsar ◽  
Khaled Sadeghi ◽  
Akio Miyamoto
Keyword(s):  
Binding Free Energy ◽  
Spike Protein ◽  
The Novel ◽  
Angiotensin Converting Enzyme 2 ◽  
Risk Of Death ◽  
Main Protease ◽  
The World ◽  
Novel Coronavirus ◽  
Very High ◽  
Potential Use

Abstract The novel coronavirus disease (COVID-19) presently poses significant concerns around the world. Latest reports show that the degree of disease and mortality of COVID-19 infected patients may vary from gender to gender with a very high risk of death for seniors. It was hypothesized that sex steroid hormones estradiol (E2), progesterone (P4), testosterone (T), and dexamethasone (DEX) may change the interaction of coronavirus spike protein (CSP) with angiotensin converting enzyme-2 (ACE2). Data showed that E2 was more strongly to interact with the main protease of the coronavirus, while T had the lowest affinity for CSP. The binding energy of the CSP to ACE2 was increased in the presence of steroids; the greatest increase was observed by DEX and E2. The binding free energy of the CSP to ACE2 was the highest in the presence of E2 and DEX. Together, the interaction between CSP and ACE2 can be disrupted by E2 and to a greater extent by DEX, in part explaining the lower incidence of COVID-19 infection in women than men. The potential use of E2 and DEX to reduce coronavirus attachment to ACE2 in the early phase of the coronavirus invasion needs to be clinically investigated.

scholarly journals Associations between female lung cancer risk and sex steroid hormones: a systematic review and meta-analysis of the worldwide epidemiological evidence on endogenous and exogenous sex steroid hormones

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hui Zeng ◽  
Zhuoyu Yang ◽  
Jiang Li ◽  
Yan Wen ◽  
Zheng Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Steroid Hormones ◽  
Lung Cancer Risk ◽  
Meta Analysis ◽  
Sex Steroid Hormones ◽  
Sex Steroid ◽  
Sex Steroid Hormone ◽  
Hormone Exposure ◽  
Female Lung Cancer

Abstract Background Published findings suggest sex differences in lung cancer risk and a potential role for sex steroid hormones. Our aim was to perform a meta-analysis to investigate the effects of sex steroid hormone exposure specifically on the risk of lung cancer in women. Methods The PubMed, MEDLINE, Web of Science, and EMBASE databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for female lung cancer risk associated with sex steroid hormones were calculated overall and by study design, publication year, population, and smoking status. Sensitivity analysis, publication bias, and subgroup analysis were performed. Results Forty-eight studies published between 1987 and 2019 were included in the study with a total of 31,592 female lung cancer cases and 1,416,320 subjects without lung cancer. Overall, higher levels of sex steroid hormones, both endogenous (OR: 0.92, 95% CI: 0.87–0.98) and exogenous (OR: 0.86, 95% CI: 0.80–0.93), significantly decreased the risk of female lung cancer by 10% (OR: 0.90, 95% CI: 0.86–0.95). The risk of lung cancer decreased more significantly with a higher level of sex steroid hormones in non-smoking women (OR: 0.88, 95% CI: 0.78–0.99) than in smoking women (OR: 0.98, 95% CI: 0.77–1.03), especially in Asia women (OR: 0.84, 95% CI: 0.74–0.96). Conclusions Our meta-analysis reveals an association between higher levels of sex steroid hormone exposure and the decreased risk of female lung cancer. Surveillance of sex steroid hormones might be used for identifying populations at high risk for lung cancer, especially among non-smoking women.

Reproductive Dysfunction in Women With Epilepsy: Antiepileptic Drug Effects on Sex-Steroid Hormones

CNS Spectrums ◽  
2001 ◽  
Vol 6 (9) ◽  
pp. 771-786 ◽  
Author(s):  
Martha J. Morrell ◽  
Kerry L. Flynn ◽  
Cairn G. Seale ◽  
Silvia Doñe ◽  
Amelia J. Paulson ◽  
...  
Keyword(s):  
At Risk ◽  
Cytochrome P450 ◽  
Steroid Hormones ◽  
Drug Effects ◽  
Free Testosterone ◽  
Sex Steroid Hormones ◽  
Sex Steroid ◽  
Cytochrome P450 Enzymes ◽  
Sex Steroid Hormone ◽  
Reproductive Aged Women

ABSTRACTWomen with epilepsy are at risk for reproductive health dysfunction. Sex-steroid hormone abnormalities have been reported in women with epilepsy, but it has been difficult to determine whether these abnormalities are due to epilepsy-related hypothalamic-pituitary axis dysfunction, or to pharmacokinetic actions of antiepileptic drugs (AEDs). Sex-steroid hormones were evaluated in 84 reproductive-aged women with epilepsy receiving an AED in monotherapy, and in 20 nonepileptic controls. Estrone, free testosterone, and androstenedione were significantly lower in subjects receiving enzyme-inducing AEDs than in nonepileptic controls. Free testosterone was significantly elevated in subjects receiving valproate compared to nonepileptic controls. Subjects with epilepsy receiving gabapentin or lamotrigine were no different from the nonepileptic controls in any of the endocrine variables. Subjects with epilepsy who are receiving AEDs that alter cytochrome P450 enzymes are at risk for significant abnormalities in sex-steroid hormones. In contrast, subjects receiving AEDs that do not alter cytochrome P450 enzymes show no differences in sex-steroid hormones compared with nonepileptic controls. With new AEDs available that do not alter cytochrome P450 enzymes, physician selection of therapy should consider not only seizure control, but also potential effects on reproductive physiology.

scholarly journals Carcinogenesis of Triple-Negative Breast Cancer and Sex Steroid Hormones

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2588
Author(s):  
Naoko Honma ◽  
Yoko Matsuda ◽  
Tetuo Mikami
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Steroid Hormones ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Steroid Receptors ◽  
Clinical Importance ◽  
Sex Steroid Hormones ◽  
Sex Steroid ◽  
Sex Steroid Hormone

Triple-negative breast cancer (TNBC) lacks an effective treatment target and is usually associated with a poor clinical outcome; however, hormone unresponsiveness, which is the most important biological characteristic of TNBC, only means the lack of nuclear estrogenic signaling through the classical estrogen receptor (ER), ER-α. Several sex steroid receptors other than ER-α: androgen receptor (AR), second ER, ER-β, and non-nuclear receptors represented by G-protein-coupled estrogen receptor (GPER), are frequently expressed in TNBC and their biological and clinical importance has been suggested by a large number of studies. Despite the structural similarity between each sex steroid hormone (androgens and estrogens) or each receptor (AR and ER-β), and similarity in the signaling mechanisms of these hormones, most studies or reviews focused on one of these receptors, and rarely reviewed them in a comprehensive way. Considering the coexistence of these hormones and their receptors in TNBC in a clinical setting, a comprehensive viewpoint would be important to correctly understand the association between the carcinogenic mechanism or pathobiology of TNBC and sex steroid hormones. In this review, the carcinogenic or pathobiological role of sex steroid hormones in TNBC is considered, focusing on the common and divergent features of the action of these hormones.

scholarly journals The impact of calcitriol and estradiol on the SARS-CoV-2 biological activity: a molecular modeling approach

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Alireza Mansouri ◽  
Rasoul Kowsar ◽  
Mostafa Zakariazadeh ◽  
Hassan Hakimi ◽  
Akio Miyamoto
Keyword(s):  
Active Site ◽  
Clinical Investigation ◽  
Host Cells ◽  
Spike Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Risk Of Death ◽  
Main Protease ◽  
Computational Data ◽  
Novel Coronavirus ◽  
The Impact

AbstractThe novel coronavirus disease (COVID-19) is currently a big concern around the world. Recent reports show that the disease severity and mortality of COVID-19 infected patients may vary from gender to gender with a very high risk of death for seniors. In addition, some steroid structures have been reported to affect coronavirus, SARS-CoV-2, function and activity. The entry of SARS-CoV-2 into host cells depends on the binding of coronavirus spike protein to angiotensin converting enzyme-2 (ACE2). Viral main protease is essential for the replication of SARS-CoV-2. It was hypothesized that steroid molecules (e.g., estradiol, progesterone, testosterone, dexamethasone, hydrocortisone, prednisone and calcitriol) could occupy the active site of the protease and could alter the interaction of spike protein with ACE2. Computational data showed that estradiol interacted more strongly with the main protease active site. In the presence of calcitriol, the binding energy of the spike protein to ACE2 was increased, and transferring Apo to Locked S conformer of spike trimer was facilitated. Together, the interaction between spike protein and ACE2 can be disrupted by calcitriol. Potential use of estradiol and calcitriol to reduce virus invasion and replication needs clinical investigation.

scholarly journals The study of sex steroid hormone compound in green algae (Chlorophyta) for female fertility: A literature review

2021 ◽  
Vol 913 (1) ◽  
pp. 012085
Author(s):  
L A Arini
Keyword(s):  
Reproductive Health ◽  
Steroid Hormones ◽  
Green Algae ◽  
Healthy Lifestyle ◽  
Cell Damage ◽  
Sex Steroid Hormones ◽  
The Body ◽  
Female Fertility ◽  
Sex Steroid ◽  
Sex Steroid Hormone

Abstract Reproductive organ cell damage due to oxidants can cause problems in female fertility, this situation can be prevented and overcome by consuming antioxidants such as algae. Green algae Chlorophyta also contains a steroid that is thought to be useful for normal reproductive health in women. The purpose of this study was to determine the compounds of sex steroid hormones in green algae which are important for female fertility. The systematic review method was used in this study. Based on the results of studies, it shows that green algae contain sterols which through biochemical mechanisms will form sex steroid hormones in the target organ. These hormones play an important role in the regulation of the female reproductive system and the balance of these hormones is crucial for normal fertility in women. Based on this, women should be able to maintain their reproductive health well by consuming foods that contain lots of vitamins and natural fibers that are good for the body such as green algae. Women must also be able to maintain a healthy lifestyle, change bad lifestyles, and avoid environmental risk factors that can cause infertility.

scholarly journals Sex steroid hormones differentially regulate CYP2D in female wild-type and CYP2D6-humanized mice

2020 ◽  
Vol 245 (2) ◽  
pp. 301-314
Author(s):  
Maria Konstandi ◽  
Christina E Andriopoulou ◽  
Jie Cheng ◽  
Frank J Gonzalez
Keyword(s):  
Steroid Hormones ◽  
Estrous Cycle ◽  
Sex Steroid Hormones ◽  
Sex Steroid ◽  
Activity Levels ◽  
Mrna Levels ◽  
Sex Steroid Hormone ◽  
17Β Estradiol ◽  
Highly Correlated ◽  
Species Specific

The CYP2D subfamily catalyses the metabolism of about 25% of prescribed drugs, including the majority of antidepressants and antipsychotics. At present, the mechanism of hepatic CYP2D regulation remains largely unknown. This study investigated the role of sex steroid hormones in CYP2D regulation. For this purpose, Cyp2d22 expression was assessed in the distinct phases of the estrous cycle of normocyclic C57BL/6J (WT) female mice. Cyp2d22 was also evaluated in ovariectomised WT and CYP2D6-humanized (hCYP2D6) mice that received hormonal supplementation with either 17β-estradiol (E2) and/or progesterone. Comparisons were also made to male mice. The data revealed that hepatic Cyp2d22 mRNA, protein and activity levels were higher at estrous compared to the other phases of the estrous cycle and that ovariectomy repressed Cyp2d22 expression in WT mice. Tamoxifen, an anti-estrogenic compound, also repressed hepatic Cyp2d22 via activation of GH/STAT5b and PI3k/AKT signaling pathways. Both hormones prevented the ovariectomy-mediated Cyp2d22 repression. In case of progesterone, this may be mediated by inhibition of the PI3k/AKT/FOX01 pathway. Notably, Cyp2d22 mRNA levels in WT males were similar to those in ovariectomised mice and were markedly lower compared to females at estrous, a differentiation potentially regulated by the GH/STAT5b pathway. Sex steroid hormone-related alterations in Cyp2d22 mRNA expression were highly correlated with Hnf1a mRNA. Interestingly, fluctuations in Cyp2d22 in hippocampus and cerebellum followed those in liver. In contrast to WT mice, ovariectomy induced hepatic CYP2D6 expression in hCYP2D6 mice, whereas E2 and/or progesterone prevented this induction. Apparently, sex steroid hormones display a significant gender- and species-specific role in the regulation of CYP2D.

scholarly journals Changes in plasma steroid hormones and gonadal histology associated with sexual maturation in wild southern hake (Merluccius australis)

2017 ◽  
Vol 43 (4) ◽  
pp. 632-640
Author(s):  
Manuel Alvarado ◽  
Edison Serrano ◽  
Juan Carlos Sánchez ◽  
Luis Valladares
Keyword(s):  
Steroid Hormones ◽  
Steroid Hormone ◽  
Sex Steroid Hormones ◽  
Sex Steroid ◽  
Sex Steroid Hormone ◽  
Asynchronous Development ◽  
Gonadal Histology ◽  
Males And Females ◽  
First Time

A detailed study of gametes development and characterization of plasma sex steroid hormones during the maturation cycle was performed for the first time in the southern hake (Merluccius australis). Fish were caught in the inland waters of the Reloncaví Sound, Interior Sea of Chiloé, Chile. Samples of gonads and blood were collected for histology and sex steroid hormone (17 β-estradiol, 11-ketotestosterone and 17,20 βdihydroxy-4-pregnen-3-one) analysis, respectively. Sex steroid hormone quantification was performed using enzyme-immunoassay (ELISA). Results showed that M. australis males and females have asynchronous development of testicles and ovaries, in all stages of maturation. Most spawning fish were found during the spring months. Regarding the sex steroid hormones, serological fluctuations of 17 β-estradiol and 11- ketotestosterone were found during gonadal maturation of M. australis. These hormones are the main hormones responsible for vitelogenesis and spermatogenesis processes, respectively. Conversely, 17,20 β-dihydroxy-4- pregnen-3-one did not show any serological fluctuation in females and males. Further studies involving gonadotropins, 17,20 β,21-trihydroxy-4-pregnen-3-one and vitellogenin quantification are required in order to obtain a more complete description of the reproductive physiology of wild and farmed M. australis.  

scholarly journals Onset of Daily Activity in a Female Songbird Is Related to Peak-Induced Estradiol Levels

2019 ◽  
Vol 59 (4) ◽  
pp. 1059-1067 ◽  
Author(s):  
Jessica L Graham ◽  
Katie B Needham ◽  
Emily M Bertucci ◽  
Alexis A Pearson ◽  
Carolyn M Bauer ◽  
...  
Keyword(s):  
Steroid Hormones ◽  
Daily Activity ◽  
Sex Steroid Hormones ◽  
Sex Steroid ◽  
Night Time ◽  
Sex Steroid Hormone ◽  
Reproductive Endocrine ◽  
Activity Onset ◽  
Highly Correlated ◽  
Endocrine Axis

Abstract Research in captive birds and mammals has demonstrated that circadian (i.e., daily) behavioral rhythms are altered in response to increases in sex-steroid hormones. Recently, we and others have demonstrated a high degree of individual repeatability in peak (gonadotropin-releasing hormone [GnRH]-induced sex) steroid levels, and we have found that these GnRH-induced levels are highly correlated with their daily (night-time) endogenous peak. Whether or not individual variation in organization and activity of the reproductive endocrine axis is related to daily timing in wild animals is not well known. To begin to explore these possible links, we tested the hypothesis that maximal levels of the sex steroid hormone estradiol (E2) and onset of daily activity are related in a female songbird, the dark-eyed junco (Junco hyemalis). We found that females with higher levels of GnRH-induced E2 departed from their nest in the morning significantly earlier than females with lower stimulated levels. We did not observe a relationship between testosterone and this measure of onset of activity. Our findings suggest an interaction between an individual’s reproductive endocrine axis and the circadian system and variation observed in an individuals’ daily activity onset. We suggest future studies examine the relationship between maximal sex-steroid hormones and timing of daily activity onset.

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