Effects of androgens on cardiovascular remodeling

Androgens, the male sex hormones, exert various biological effects on many target organs through the transcriptional effects of the nuclear androgen receptor (AR). ARs are expressed not only in classical target organs, such as the brain, genital organs, bone, and skeletal muscles, but also in the cardiovascular system. Because the female sex hormones estrogens are well-known to protect against cardiovascular disease, sex has been considered to have a significant clinical impact on cardiovascular mortality. However, the influence of androgens on the cardiovascular system has not been fully elucidated. To clarify this issue, we analyzed the effects of administration of angiotensin II and doxorubicin, an anticancer agent, in a loading model in male wild-type and AR-deficient mice. In this review, we focus on the actions of androgens as potential targets for the prevention of cardiovascular diseases in males.

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CCR5 deficiency decreases susceptibility to experimental cerebral malaria

Blood ◽

10.1182/blood-2002-05-1493 ◽

2003 ◽

Vol 101 (11) ◽

pp. 4253-4259 ◽

Cited By ~ 82

Author(s):

Elodie Belnoue ◽

Michèle Kayibanda ◽

Jean-Christophe Deschemin ◽

Mireille Viguier ◽

Matthias Mack ◽

...

Keyword(s):

T Cells ◽

Cerebral Malaria ◽

Cd8 T Cells ◽

Cytokine Production ◽

Wild Type ◽

Experimental Cerebral Malaria ◽

Pathologic Features ◽

Th1 Cytokine ◽

The Brain ◽

Deficient Mice

Abstract Infection of susceptible mouse strains with Plasmodium berghei ANKA (PbA) is a valuable experimental model of cerebral malaria (CM). Two major pathologic features of CM are the intravascular sequestration of infected erythrocytes and leukocytes inside brain microvessels. We have recently shown that only the CD8+ T-cell subset of these brain-sequestered leukocytes is critical for progression to CM. Chemokine receptor–5 (CCR5) is an important regulator of leukocyte trafficking in the brain in response to fungal and viral infection. Therefore, we investigated whether CCR5 plays a role in the pathogenesis of experimental CM. Approximately 70% to 85% of wild-type and CCR5+/- mice infected with PbA developed CM, whereas only about 20% of PbA-infected CCR5-deficient mice exhibited the characteristic neurologic signs of CM. The brains of wild-type mice with CM showed significant increases in CCR5+ leukocytes, particularly CCR5+ CD8+ T cells, as well as increases in T-helper 1 (Th1) cytokine production. The few PbA-infected CCR5-deficient mice that developed CM exhibited a similar increase in CD8+ T cells. Significant leukocyte accumulation in the brain and Th1 cytokine production did not occur in PbA-infected CCR5-deficient mice that did not develop CM. Moreover, experiments using bone marrow (BM)–chimeric mice showed that a reduced but significant proportion of deficient mice grafted with CCR5+ BM develop CM, indicating that CCR5 expression on a radiation-resistant brain cell population is necessary for CM to occur. Taken together, these results suggest that CCR5 is an important factor in the development of experimental CM.

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Virtual screening attributes male biased COVID-19 mortality to predicted antiviral activity of female sex hormones

Letters in Drug Design & Discovery ◽

10.2174/1570180818666210528153844 ◽

2021 ◽

Vol 18 ◽

Author(s):

Galal Yahya ◽

Basem Mansour ◽

Kristina Keuper ◽

Moataz Shaldam ◽

Ahmed El-Baz

Keyword(s):

Virtual Screening ◽

Sex Hormones ◽

Hospital Admissions ◽

Epidemiological Data ◽

Antiviral Effect ◽

Sex Hormone ◽

Female Sex ◽

Female Sex Hormones ◽

Disaggregated Data ◽

Male Sex

Background: Coronavirus disease-19 (COVID-19) is a newly emerged pandemic leading to a state of international alert with millions of infected individuals and thousands of deaths all over the world. Analysis of statistics and epidemiological data for the pandemic outcome pinpointed a puzzling influence of human sex on the heterogeneous outcome of COVID-19, where hospital admissions and mortality were higher among males than females. Two theories explained the observed male-biased COVID-19 mortality based on either dosage of immunoregulatory genes coded in X- chromosomes or on the abundance of the angiotensin-converting enzyme two (ACE2) receptors in males than females. Objective: In our study, we propose a third scenario through virtual screening of direct antiviral effects of sex hormones. Materials & Methods: Updated screening statistics from 47 countries displaying sex-disaggregated data on COVID-19 were employed and visualized in the form of heatmaps depicting sex difference effects on statistics of cases and deaths. Molecular docking and binding simulations of investigated sex steroids against COVID-19 specific proteins were investigated. Results: Analysis of COVID-19 sex-disaggregated data confirmed that male-biased mortality and computer-aided docking found unexpected female sex hormones biased binding against key targets implicated in the life cycle of COVID-19 compared to the male sex hormone testosterone. Other investigated steroids showed promising docking scores, while the male sex hormone exhibited the lowest affinity. Conclusion: Female sex hormones virtually exhibited direct COVID-19 effect. The proposed antiviral effect of sex hormones should be considered to explain the outcomes of mortality; moreover, the fluctuation of sex hormones influences sex and personal derived-differential response to COVID-19 infection.

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CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

Journal of Virology ◽

10.1128/jvi.79.21.13509-13518.2005 ◽

2005 ◽

Vol 79 (21) ◽

pp. 13509-13518 ◽

Cited By ~ 31

Author(s):

Jürgen Hausmann ◽

Axel Pagenstecher ◽

Karen Baur ◽

Kirsten Richter ◽

Hanns-Joachim Rziha ◽

...

Keyword(s):

T Cells ◽

Disease Virus ◽

Cd8 T Cells ◽

Gamma Interferon ◽

Wild Type ◽

Borna Disease Virus ◽

Ifn Γ ◽

The Brain ◽

Deficient Mice ◽

Borna Disease

ABSTRACT Borna disease virus (BDV) frequently causes meningoencephalitis and fatal neurological disease in young but not old mice of strain MRL. Disease does not result from the virus-induced destruction of infected neurons. Rather, it is mediated by H-2 k -restricted antiviral CD8 T cells that recognize a peptide derived from the BDV nucleoprotein N. Persistent BDV infection in mice is not spontaneously cleared. We report here that N-specific vaccination can protect wild-type MRL mice but not mutant MRL mice lacking gamma interferon (IFN-γ) from persistent infection with BDV. Furthermore, we observed a significant degree of resistance of old MRL mice to persistent BDV infection that depended on the presence of CD8 T cells. We found that virus initially infected hippocampal neurons around 2 weeks after intracerebral infection but was eventually cleared in most wild-type MRL mice. Unexpectedly, young as well as old IFN-γ-deficient MRL mice were completely susceptible to infection with BDV. Moreover, neurons in the CA1 region of the hippocampus were severely damaged in most diseased IFN-γ-deficient mice but not in wild-type mice. Furthermore, large numbers of eosinophils were present in the inflamed brains of IFN-γ-deficient mice but not in those of wild-type mice, presumably because of increased intracerebral synthesis of interleukin-13 and the chemokines CCL1 and CCL11, which can attract eosinophils. These results demonstrate that IFN-γ plays a central role in host resistance against infection of the central nervous system with BDV and in clearance of BDV from neurons. They further indicate that IFN-γ may function as a neuroprotective factor that can limit the loss of neurons in the course of antiviral immune responses in the brain.

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Sporting success among women with different set of sex characteristics

Medicine and Physical Education: Science and Practice ◽

10.20310/2658-7688-2020-2-1(5)-76-81 ◽

2020 ◽

pp. 76-81

Author(s):

Tatiana S. SOBOLEVA ◽

Dmitry V. SOBOLEV

Keyword(s):

Sex Hormones ◽

Sexual Differentiation ◽

Subsequent Development ◽

Sex Characteristics ◽

Pathological State ◽

Special Role ◽

Prenatal Period ◽

Adrenogenital Syndrome ◽

Male Sex ◽

The Brain

Success of sportswomen closely connects with peculiarities of formation of characteristics dependent on sex. Sexual differentiation of the brain from the intrauterine period is particularly important. Male sex hormones (androgens) play a special role in this process. Congenital adrenogenital syndrome forms prenatal increase of their concentration. This adrenal pathology in the mother or inherited in the girl creates a pathological state of hyperandrogenia (excessive content of androgens). This pathology forms a maskulinization (similar to a man) of the state of the female organism. Such a feature begins with a prenatal period followed by activation especially during puberty. Maskulinization of the girl's body is an important prerequisite for sports from childhood with subsequent development in adulthood.

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A Revised Role for P-Glycoprotein in the Brain Distribution of Dexamethasone, Cortisol, and Corticosterone in Wild-Type and ABCB1A/B-Deficient Mice

Endocrinology ◽

10.1210/en.2008-0041 ◽

2008 ◽

Vol 149 (10) ◽

pp. 5244-5253 ◽

Cited By ~ 40

Author(s):

Brittany L. Mason ◽

Carmine M. Pariante ◽

Sarah A. Thomas

Keyword(s):

Brain Distribution ◽

Wild Type ◽

P Glycoprotein ◽

The Brain ◽

Deficient Mice

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Human endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors

10.1101/721241 ◽

2019 ◽

Author(s):

Paul Dembny ◽

Andrew G. Newman ◽

Manvendra Singh ◽

Michael Hinz ◽

Michal Szczepek ◽

...

Keyword(s):

Endogenous Retrovirus ◽

Endogenous Retroviruses ◽

Human Endogenous Retrovirus ◽

Toll Like Receptor ◽

Wild Type ◽

Endogenous Ligand ◽

Human Endogenous Retroviruses ◽

Retroviral Transcripts ◽

The Brain ◽

Deficient Mice

AbstractAlthough human endogenous retroviruses (HERVs) represent a substantial proportion of the human genome and some HERVs have been suggested to be involved in neurological disorders, little is known about their biological function and pathophysiological relevance. HERV-K(HML-2) comprises evolutionarily young proviruses transcribed in the brain. We report that RNA derived from an HERV-K(HML-2) env gene region binds to the human RNA-sensing Toll-like receptor (TLR) 8, activates human TLR8, as well as murine Tlr7, and causes neurodegeneration through TLR8 and Tlr7 in neurons and microglia. HERV-K(HML-2) RNA introduced extracellularly into the cerebrospinal fluid (CSF) of either C57BL/6 wild-type mice or APPPS1 mice, a mouse model for Alzheimer’s disease (AD), resulted in neurodegeneration. Tlr7-deficient mice were protected against neurodegenerative effects, but were re-sensitized towards HERV-K(HML-2) RNA when neurons ectopically expressed murine Tlr7 or human TLR8. Accordingly, transcriptome datasets of human brain samples from AD patients revealed a specific correlation of upregulated HERV-K(HML-2) and TLR8 RNA expression. HERV-K(HML-2) RNA was detectable more frequently in CSF from AD individuals compared to controls. Our data establish HERV-K(HML-2) RNA as an endogenous ligand for human TLR8 and murine Tlr7 and imply a functional contribution of specific human endogenous retroviral transcripts to neurodegenerative processes such as AD.

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THE PHYSIOLOGICAL RESPONSE OF PROSTATIC AND VESICULAR TRANSPLANTS IN THE ANTERIOR CHAMBER OF THE EYE

Journal of Experimental Medicine ◽

10.1084/jem.66.3.281 ◽

1937 ◽

Vol 66 (3) ◽

pp. 281-289 ◽

Cited By ~ 7

Author(s):

Robert A. Moore ◽

Robert H. Melchionna ◽

S. H. Tolins ◽

H. B. Rosenblum

Keyword(s):

Anterior Chamber ◽

Sex Hormones ◽

Sex Hormone ◽

Moderate Increase ◽

Alkaline Extract ◽

Female Sex ◽

Female Sex Hormones ◽

Pregnancy Urine ◽

Male Sex

1. With a photographic method for the determination of the size of prostatic and vesicular transplants in the anterior chamber of the eye, it has been possible to follow continuously the response to an injection of a hormone. 2. The results may be briefly summarized as follows: (a) One injection of the gonadotropic substance of pregnancy urine produces a moderate increase in size; (b) subsequent injections of this same substance for a period of at least 3 months are without effect; (c) an alkaline extract of the whole anterior pituitary gland produces a similar increase; (d) all pituitary derivatives are ineffective in the castrated animal; (e) castration brings about a decrease in size that gradually loses velocity; (f) the male sex hormone produces a slight increase in intact, and a variable, at times conspicuous, increase in castrated animals; (g) the female sex hormone provokes a conspicuous increase in both intact and castrated animals; (h) the hormone of the corpus luteum has no effect; and (i) there is no evidence of synergism of the pituitary and male sex hormones nor of antagonism of the male and female sex hormones in adult rabbits.

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Gamma Interferon-Induced Inhibition ofToxoplasma gondii in Astrocytes Is Mediated by IGTP

Infection and Immunity ◽

10.1128/iai.69.9.5573-5576.2001 ◽

2001 ◽

Vol 69 (9) ◽

pp. 5573-5576 ◽

Cited By ~ 96

Author(s):

Sandra K. Halonen ◽

Gregory A. Taylor ◽

Louis M. Weiss

Keyword(s):

Immunoblot Analysis ◽

Significant Inhibition ◽

Gamma Interferon ◽

Wild Type ◽

Effector Cells ◽

Inhibition Of Growth ◽

The Central Nervous System ◽

Ifn Γ ◽

The Brain ◽

Deficient Mice

ABSTRACT Toxoplasma gondii is an important pathogen in the central nervous system, causing a severe and often fatal encephalitis in patients with AIDS. Gamma interferon (IFN-γ) is the main cytokine preventing reactivation of Toxoplasma encephalitis in the brain. Microglia are important IFN-γ-activated effector cells controlling the growth of T. gondii in the brain via a nitric oxide (NO)-mediated mechanism. IFN-γ can also activate astrocytes to inhibit the growth of T. gondii. Previous studies found that the mechanism in murine astrocytes is independent of NO and all other known anti-Toxoplasma mechanisms. In this study we investigated the role of IGTP, a recently identified IFN-γ-regulated gene, in IFN-γ inhibition of T. gondii in murine astrocytes. Primary astrocytes were cultivated from IGTP-deficient mice, treated with IFN-γ, and then tested for anti-Toxoplasma activity. In wild-type astrocytesT. gondii growth was significantly inhibited by IFN-γ, whereas in astrocytes from IGTP-deficient mice IFN-γ did not cause a significant inhibition of growth. Immunoblot analysis confirmed that IFN-γ induced significant levels of IGTP in wild-type murine astrocytes within 24 h. These results indicate that IGTP plays a central role in the IFN-γ-induced inhibition of T. gondii in murine astrocytes.

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Vaccine-induced protection against Borna disease in wild-type and perforin-deficient mice

Journal of General Virology ◽

10.1099/vir.0.80566-0 ◽

2005 ◽

Vol 86 (2) ◽

pp. 399-403 ◽

Cited By ~ 17

Author(s):

Jürgen Hausmann ◽

Karen Baur ◽

Karin R. Engelhardt ◽

Timo Fischer ◽

Hanns-Joachim Rziha ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Neurological Disease ◽

Cell Epitope ◽

Wild Type ◽

Immune Priming ◽

Boost Immunization ◽

The Brain ◽

Deficient Mice ◽

Borna Disease

Borna disease virus (BDV) can persistently infect the central nervous system and induce CD8+ T-cell-mediated neurological disease in MRL mice. To determine whether specific immune priming would prevent disease, a prime–boost immunization protocol was established in which intramuscular injection of a recombinant parapoxvirus expressing BDV nucleoprotein (BDV-N) was followed by intraperitoneal infection with vaccinia virus expressing BDV-N. Immunized wild-type and perforin-deficient mice remained healthy after intracerebral infection with BDV and contained almost no virus in the brain at 5 weeks post-challenge. Immunization failed to induce resistance against BDV in mice lacking mature CD8+ T cells. Immunization of perforin-deficient mice with a poxvirus vector expressing mutant BDV-N lacking the known CD8+ T-cell epitope did not efficiently block multiplication of BDV in the brain and did not prevent neurological disease, indicating that vaccine-induced immunity to BDV in wild-type and perforin-deficient mice resulted from the action of CD8+ T cells.

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