Ar-receptor

BACKGROUND: Spironolactone (SPI) is a diuretic widely used to treat cardiovascular diseases (CVD) and is non-specific for mineralocorticoid receptors (MR) and with an affinity for progesterone (PR) and androgen (AR) receptors. Since 2009, it has been suggested that pharmaceuticals are emerging contaminants (called EDC), and recently, it was reported that most EDC are AR and MR antagonists and estrogen receptors (ER) agonists. Concerning SPI, endocrine-disrupting effects were observed in female western mosquitofish, but there are still no data regarding the SPI effects as a possible human EDC...

OBJECTIVES: The aim of this study was to evaluate the expression profile of sex steroid receptors and redox mediators in the uterus of domestic cats with pyometra. METHODS: Twelve cats were used and divided into groups: (1) non-gestational healthy diestrus (n = 7) and (2) pyometra (n = 5). The plasma profiles of estradiol and progesterone (P4 ) as well as uterine expression levels of estradiol alpha (ERα), progesterone (PR) and androgen (AR) receptors, of the antioxidant enzymes superoxide dismutase 1 (SOD1), catalase and glutathione peroxidase 1 (GPX1), and of the oxidative damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) were evaluated...

INTRODUCTION: As a global public health crisis, antibiotic resistance (AR) should be monitored and managed under the One-Health concept according to the World Health Organization (WHO), considering the interconnection between humans, animals, and the environment. But this approach often remains focused on human health and rarely on the environment and its compartments, especially wastewater as the main AR receptor. Wastewater treatment plants (WWTPs) not only are not designed for reliving AR but also provide appropriate conditions for enhancing AR through different mechanisms...

Prostate Cancer (PCa) is an abnormal cell growth within the prostate. This condition is the second most widespread malignancy in elderly males and one of the most frequently diagnosed life-threatening conditions. The Androgen receptor signaling pathway played a crucial role in the initiation and spread to increase the risk of PCa. Hence, targeting the AR receptor signaling pathway is a key strategy for a therapeutic plan for PCa. Our study focuses on recognizing potential inhibitors for dual targeting in PCa by using the in-silico approach...

Lead (Pb) is an emerging contaminant widely distributed in aquatic environments, which has serious effects on human and animal health. In this study, we determined whether Pb exposure affects gametogenesis, sex steroids, estrogen (ERα and ERβ), and androgen (AR) receptors. Adult specimens of Astyanax bimaculatus were exposed in duplicate to 15, 50, and 100 μg/L of lead acetate, whereas the control group was not exposed. After 28 days of exposure, fish were euthanized and samples of the gonads, liver, and blood were collected for analysis...

INTRODUCTION: The third-generation of aromatase inhibitors (AIs)-Exemestane (Exe), Letrozole (Let), and Anastrozole (Ana)-is the main therapeutic approach applied for estrogen receptor-positive (ER+) breast cancer (BC), the most common neoplasm in women worldwide. Despite their success, the development of resistance limits their efficacy. Genistein (G), a phytoestrogen present in soybean, has promising anticancer properties in ER+ BC cells, even when combined with anticancer drugs. Thus, the potential beneficial effects of combining G with AIs were investigated in sensitive (MCF7-aro) and resistant (LTEDaro) BC cells...

Anabolic androgenic steroids (AAS) are substances with androgenic and anabolic characteristics. Among the many side effects of hormone therapy with AAS, the following stand out: heart problems, adrenal gland disorders, aggressive behavior, increased risk of prostate cancer, problems related to lack of libido and impotence. Such substances vary in the relationship between androgenic activity, and the activation of the androgen receptor (AR) is of fundamental importance for the singularity of the action of each AAS...

BACKGROUND: Although estrogen (ERα/ERβ), progesterone (PGR), and androgen (AR) receptors are pathologically altered in colorectal cancer (CRC), their simultaneous expression within the same cohort of patients was not previously measured. METHODS: ERα/ERβ/PGR/AR proteins were measured in archived paired normal and malignant colon specimens (n =120 patients) by immunohistochemistry, and results were analyzed by gender, age (≤50 vs. ≥60 years), clinical stages (early-stage I/II vs...

Sex steroids and antioxidant enzymes are important in female sexual development and adequate modulation of the estrous cycle, pregnancy, and fetal development. Therefore, modifications in its signaling or expression in the genital system are associated with reproductive dysfunctions. However, the spatial-temporal expression profile of receptors for sex steroids and antioxidant enzymes in the uterus of domestic cats throughout the estrous cycle needs to be studied. Cats in proestrus/estrus (N = 6), diestrus, (N = 7), and anestrus (N = 6) were used to evaluate the uterine expression of estrogen alpha (ERα), progesterone (PR), and androgen (AR) receptors and of the antioxidant enzymes superoxide dismutase 1 (SOD1), catalase and glutathione peroxidase 1 (GPX1) by immunohistochemistry and qPCR...

Cancer is the leading cause of death and represents a significant economic burden worldwide. The numbers are constantly growing as a result of increasing life expectancy, toxic environmental factors, and adoption of Western lifestyle. Among lifestyle factors, stress and the related signaling pathways have recently been implicated in the development of tumors. Here we present some epidemiological and preclinical data concerning stress-related activation of the ß-adrenoreceptors (ß-ARs), which contributes to the formation, sequential transformation, and migration of different tumor cell types...

G protein-coupled receptors (GPCR) activate numerous intracellular signaling pathways. The oligomerization properties of GPCRs, and hence their cellular functions, may be modulated by various components within the cell membrane (such as the presence of cholesterol). Modulation may occur directly via specific interaction with the GPCR or indirectly by affecting the physical properties of the membrane. Here, we use pulsed Q-band double electron-electron resonance (DEER) spectroscopy to probe distances between R1 nitroxide spin labels attached to Cys163 and Cys344 of the β1 -adrenergic receptor (β1 AR) in n -dodecyl-β-D-maltoside micelles upon titration with two soluble cholesterol analogs, cholesteryl hemisuccinate (CHS) and sodium cholate...

With the objective to develop a potential 99m Tc radiopharmaceutical for imaging the androgen receptor (AR) in prostate cancer, four ligands bearing the same pharmacophore derived from the AR antagonist flutamide were prepared, labeled with 99m Tc, and their structures corroborated via comparison with the corresponding stable rhenium analogs. All complexes were obtained with high radiochemical purity. Three of the complexes were highly stable, and, due to their favorable physicochemical properties, were further evaluated using AR-positive and AR-negative cells in culture...

BACKGROUND: Acute lung injury (ALI) is a serious condition. Inflammation plays a crucial role in the pathogenesis of ALI. Cupping, as a part of traditional Chinese medicine, is still a popular complementary and alternative therapy for a variety of ailments including respiratory diseases. However, reliable scientific data about cupping therapy are scarce. Adenosine, a purine nucleoside produced under metabolic stress by the action of extracellular ectonucleotidases (i.e. CD39 and CD73), can attenuate ALI through the A2B AR receptor...

Prostate cancer (PCa) is a malignant tumor with a higher mortality rate in the male reproductive system. In this study, the hydroxyazine derivatives were synthesized with different structure from traditional anti-prostate cancer drugs. In the evaluation of in vitro cytotoxicity and antagonistic activity of PC-3, LNCaP, DU145 and androgen receptor, it was found that the mono-substituted derivatives on the phenyl group ( 4 , 6 , 7 , and 9 ) displayed strong cytotoxic activities, and compounds 11 - 16 showed relatively strong antagonistic potency against AR (Inhibition% >55)...

The female reproductive system which consists of the ovaries, uterus (myometrium, endometrium), Fallopian tubes, cervix and vagina is exquisitely sensitive to the actions of steroid hormones. The ovaries play a key role in the synthesis of bioactive steroids (oestrogens, androgens, progestins) that act both within the tissue (intracrine/paracrine) as well as on other reproductive organs following release into the blood stream (endocrine action). Sex steroid receptors encoded by the oestrogen (ESR1, ESR2), progesterone (PR) and androgen (AR) receptor genes, which are members of the superfamily of ligand activated transcription factors are widely expressed within these tissues...

G-protein coupled receptors (GPCRs) have been largely targeted in a wide range of diseases, but few therapies have been directed against GPCRs in the field of cancer, partly because of the lack of effective target identification strategies. Here, using colorectal cancer (CRC) as a model, we explored the gene expression of a panel of GPCRs in tumor and stromal cells, identifying specific gene sets defining each cellular compartment. We selected the adenosine receptor 2B (A2B AR), specifically expressed in cancer cell lines compared with stromal cells, to explore the use of fluorescent ligands that can be used for target visualization...

Numerous experiments have revealed that fullerene (C60 ) and its derivatives can bind to proteins and affect their biological functions. In this study, we explored the interaction between fullerine and the β2 -adrenergic receptor (β2 AR). The MD simulation results show that fullerene binds with the extracellular loop 2 (ECL2) and intracellular loop 2 (ICL2) of β2 AR through hydrophobic interactions and π-π stacking interactions. In the C60 _in1 trajectory, due to the π-π stacking interactions of fullerene molecules with PHE and PRO residues on ICL2, ICL2 completely flipped towards the fullerene direction and the fullerene moved slowly into the lipid membrane...

The aldose reductase (AR) enzyme is an important target enzyme in the development of therapeutics against hyperglycaemia induced health complications such as retinopathy, etc. In the present study, a quantitative structure activity relationship (QSAR) evaluation of a dataset of 226 reported AR inhibitor (ARi) molecules is performed using a genetic algorithm - multi linear regression (GA-MLR) technique. Multi-criteria decision making (MCDM) analysis furnished two five variables based QSAR models with acceptably high performance reflected in various statistical parameters such as, R2  = 0...

BACKGROUND: Beta-adrenergic (β-AR) receptor blockers (BBs) are an essential class of drugs as they have numerous indications. On the other hand, they have numerous unwanted effects which decrease the compliance, adherence, and persistence of this very useful group of drugs. OBJECTIVE: The paper aims to analyze the possibility that an unnoticed side effect may contribute to a less favorable pharmacologic profile of BBs, e.g., a diminished reaction to a sudden fall in BP...

Activation of a specific protein kinase C (PKC) isoform during stimulation of Gq protein-coupled receptors (Gq PCRs) is determined by homologous receptor desensitization that controls the spatiotemporal formation of downstream Gq signalling molecules. Furthermore, Gq PCR-activated PKC isoforms specifically regulate receptor activity via a negative feedback mechanism. In the present study, we investigated the contribution of several phosphorylation sites in the α1B -adrenergic receptor (α1B -AR) for PKC and G protein coupled receptor kinase 2 (GRK2) to homologous receptor desensitization and effector modulation...