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Androgen receptor

Marie C Hupe, M Raschid Hoda, Friedemann Zengerling, Sven Perner, Axel S Merseburger, Marcus V Cronauer
OBJECTIVE: The bromodomain and extra-terminal (BET) family of proteins provides a scaffolding platform for the recruitment and tethering of transcription factors to acetylated chromatin, thereby modulating gene expression. In this study, we evaluated the efficacy of the BET-inhibitor PFI-1 to diminish AR/AR-V7 signaling and proliferation in castration-resistant prostate cancer cells. METHODS: Prostate-specific antigen and androgen receptor (AR) protein were quantified by means of two commercial ELISAs...
June 22, 2018: World Journal of Urology
Jianzhuo Li, Xueqi Fu, Subing Cao, Jing Li, Shu Xing, Dongying Li, Yan Dong, Derrick Landon Cardin, Hee-Won Park, Franck Mauvais-Jarvis, Haitao Zhang
The androgen receptor (AR) is a ligand-activated nuclear receptor that plays a critical role in normal prostate physiology, as well as in the development and progression of prostate cancer. In addition to the classical paradigm in which AR exerts its biological effects in the nucleus by orchestrating the expression of the androgen-regulated transcriptome, there is considerable evidence supporting a rapid, non-genomic activity mediated by membrane-associated AR. Although the genomic action of AR has been studied in depth, the molecular events governing AR transport to the plasma membrane and the downstream AR signaling cascades remain poorly understood...
June 22, 2018: Journal of Biological Chemistry
Putri Ayu Jayusman, Isa Naina Mohamed, Ekram Alias, Norazlina Mohamed, Ahmad Nazrun Shuid
Male osteoporosis is associated with higher rates of disability and mortality. Hence the search for suitable intervention and treatment to prevent the degeneration of skeletal health in men is necessary. Eurycoma longifolia (EL), a traditional plant with aphrodisiac potential may be used to treat and prevent male osteoporosis. The skeletal protective effect of quassinoid-rich EL extract, which has a high content of eurycomanone, has not been studied. This study aimed to determine whether EL could prevent skeletal deteriorations in gonadal hormone-deficient male rats...
June 21, 2018: Nutrients
R Basak, A Roy, U Rai
This study of spotted snakehead Channa punctata was aimed to develop a comprehensive understanding of testicular gonadotropin receptors, from their sequence characterization, temporal expression to gonadotropic regulation, in seasonally breeding teleosts. A single form of follicle-stimulating hormone receptor (cpfshra) and luteinizing hormone-choriogonadotropin receptor (cplhcgr), was identified from testicular transcriptome data of C. punctata. Although deduced full-length protein sequence for cpFshra (694 amino acids) and cpLhcgr (691 amino acids) showed homology with their counterparts of other vertebrates, multiple insertion-deletion-substitution of residues suggest marked alterations in their structure and ligand specificity...
June 21, 2018: Journal of Fish Biology
Qun Rao, Huiping Zhang, Cuantai Zhang, Qianyuan Zhuang, Guanghui Du, Shaogang Wang, Zhangqun Ye, Yuan Chen
As an important component in the innate immune system, natural killer (NK) cells have been demonstrated to be clinically associated with prostate cancer (PCa) progression and castration resistance. Therefore, the development of novel agents that may enhance the cytotoxicity of NK cells possesses promising therapeutic applications. In the present study, leinal polypeptide (LP) solution was supplemented into a co-culture system of NK and PCa cells, as it was previously demonstrated that LP are able to activate NK cells, which kill PCa cells based on an MTT cell viability assay...
July 2018: Oncology Letters
Lucile Noyer, Guillaume P Grolez, Natalia Prevarskaya, Dimitra Gkika, Loic Lemonnier
While originally cloned from the prostate in 2001, transient receptor potential, melastatin member 8 (TRPM8) has since been identified as the cold/menthol receptor in the peripheral nervous system. This discovery has led to hundreds of studies regarding the role of this channel in pain and thermosensation phenomena, while relegating TRPM8 involvement in cancer to a secondary role. Despite these findings, there is growing evidence that TRPM8 should be carefully studied within the frame of carcinogenesis, especially in the prostate, where it is highly expressed and where many teams have confirmed variations in its expression during cancer progression...
June 20, 2018: Pflügers Archiv: European Journal of Physiology
Li-Jun Yin, Xiao-Hui Wang
Recently, there has been a growing interest in the roles of androgen in the development of obesity and obesity-related diseases such as diabetes, metabolic syndrome, atherosclerosis (AS), hypertension and cardiovascular diseases, as well as in the disorders of glucose and lipid metabolism. Androgen exerts its biological role mainly through binding to the androgen receptor (AR), one of the nuclear receptors widely expressed in multiple tissues such as the skeletal muscle, liver, adipose tissue and brain. Low testosterone and AR deficiency result in obesity, obesity-related diseases and metabolic disorders...
June 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Guadalupe Navarro, Camille Allard, Jamie J Morford, Weiwei Xu, Suhuan Liu, Adrien Jr Molinas, Sierra M Butcher, Nicholas Hf Fine, Manuel Blandino-Rosano, Venkata N Sure, Sangho Yu, Rui Zhang, Heike Münzberg, David A Jacobson, Prasad V Katakam, David J Hodson, Ernesto Bernal-Mizrachi, Andrea Zsombok, Franck Mauvais-Jarvis
Androgen excess predisposes women to type 2 diabetes (T2D), but the mechanism of this is poorly understood. We report that female mice fed a Western diet and exposed to chronic androgen excess using dihydrotestosterone (DHT) exhibit hyperinsulinemia and insulin resistance associated with secondary pancreatic β cell failure, leading to hyperglycemia. These abnormalities are not observed in mice lacking the androgen receptor (AR) in β cells and partially in neurons of the mediobasal hypothalamus (MBH) as well as in mice lacking AR selectively in neurons...
June 21, 2018: JCI Insight
Sean C Skeldon, Bruce Carleton, James Brophy, Mohit Sodhi, Mahyar Etminan
OBJECTIVE: Case reports have suggested an increased risk of gynecomastia with HMG-CoA reductase inhibitors (i.e. statins). A recent meta-analysis also found that statins decrease circulating testosterone levels in men. We investigated whether statin use was associated with an increased risk of gynecomastia. DESIGN: Case control study. PATIENTS: A cohort of patients from a random sample of 9,053,240 US subjects from the PharMetrics Plus™ health claims database from 2006 to 2016 was created...
June 19, 2018: Clinical Endocrinology
Daniel J Tobiansky, Kathryn G Wallin-Miller, Stan B Floresco, Ruth I Wood, Kiran K Soma
Multiple lines of evidence indicate that androgens, such as testosterone, modulate the mesocorticolimbic system and executive function. This review integrates neuroanatomical, molecular biological, neurochemical, and behavioral studies to highlight how endogenous and exogenous androgens alter behaviors, such as behavioral flexibility, decision making, and risk taking. First, we briefly review the neuroanatomy of the mesocorticolimbic system, which mediates executive function, with a focus on the ventral tegmental area (VTA), nucleus accumbens (NAc), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC)...
2018: Frontiers in Endocrinology
Adam G Sowalsky, Huihui Ye, Manoj Bhasin, Eliezer M Van Allen, Massimo Loda, Rosina T Lis, Laleh Montaser-Kouhsari, Carla Calagua, Fen Ma, Joshua W Russo, Rachel J Schaefer, Olga S Voznesensky, Zhenwei Zhang, Glenn J Bubley, Bruce Montgomery, Elahe A Mostaghel, Peter S Nelson, Mary-Ellen Taplin, Steven P Balk
Primary prostate cancer (PCa) can have extensive microheterogeneity, but its contribution to the later emergence of metastatic castration-resistant PCa (mCRPC) remains unclear. In this study, we microdissected residual PCa foci in radical prostatectomies from 18 men treated with neoadjuvant intensive androgen deprivation therapy (leuprolide, abiraterone acetate, and prednisone) and analyzed them for resistance mechanisms. Transcriptome profiling showed reduced but persistent androgen receptor (AR) activity in residual tumors with no increase in neuroendocrine differentiation...
June 19, 2018: Cancer Research
Mandar Ankolkar, Sharvari S Deshpande, Nafisa H Balasinor
Sperm chromatin packaging is a very complex and highly regulated phenomenon. While most of the sperm chromatin is replaced by protamines, some are retained in nucleosomes. It is recently being recognised that these nucleosomes are intentionally retained and could be contributing to the expression of genes in the very early stages of embryogenesis. Endocrine disruption has been previously shown to affect reproductive outcome and sperm DNA methylation. This study aims to decipher the possibility of changes in nucleosome occupancy in sperm chromatin, induced by tamoxifen (selective oestrogen receptor modulator) and cyproterone acetate (androgen antagonist)...
June 19, 2018: Andrologia
Naglaa A Mostafa, Magda Assaf, Sami Elhakim, Mona R E Abdel-Halim, Eman El-Nabarawy, Khaled Ghareeb
BACKGROUND: The distinction of trichoepithelioma from basal cell carcinoma in small superficial biopsies is important but often challenging. This has inspired many scientists to test the validity of immunohistochemical markers in the differential diagnosis. OBJECTIVES: to develop an immunohistochemical protocol that helps in differentiation between both TE and BCC with higher sensitivity and specificity. METHODS: Using standard immunohistochemical techniques, we examined 10 TEs and 19 BCCs for the expression of CK19, Ki67, Androgen receptors (AR), CD10, and PHLDA1...
June 19, 2018: Journal of Cutaneous Pathology
Xiaowei Diao, Xiubin Chen, Yurui Pi, Yu Zhang, Fangfang Wang, Ping Liu, Yanhong Gao, Xiaojun Wang, Sijun Yang, Shan Lu
Erythropoietin‑producing hepatocellular carcinoma cell surface type‑A receptor 3 (EPHA3) has been found to promote the proliferation and survival of prostate cancer (PCa) cell lines and prostate tumor development in nude mice. However, the regulation of EPHA3 in PCa remains largely unknown. This study is aimed to investigate the association between EPHA3 expression and androgen receptor (AR) signaling and the potential mechanism. We determined mRNA and protein levels of EPHA3 and AR signaling‑related genes in the PCa cell line 22Rv1 by reverse transcription‑polymerase chain reaction (RT‑PCR) and western blotting, respectively...
June 18, 2018: Oncology Reports
Meng Xu, Huamao Jaing, Haiguang Wang, Jiajie Liu, Baohao Liu, Zhongqiang Guo
The mechanisms of malignant cell metastasis to secondary sites are complex and multifactorial. Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis. SIBLINGs promote malignant cell invasion and metastasis by enhancing matrix metalloproteinase 2 (MMP‑2) and MMP‑9 expression. Moreover, BSP and OPN can combine with integrin, which is located on the tumor cell surface, to further promote the malignant behavior of tumor cells...
June 18, 2018: Oncology Reports
Yongbo Song, Chao Song, Sixing Yang
MiR-30d-5p, a member of the microRNA family, was recently reported to regulate androgen receptor signaling in prostate cancer (PCa). Ecto-5'-nucleotidase (NT5E/CD73) is a pivotal regulator of tumor migration and has angiogenetic properties. However, the undiscovered function of miR-30d-5p and whether it targeted NT5E in PCa remain uncertain. In this study, the authors observed miR-30d-5p was significantly downregulated in PCa tissues and cell lines compared with the adjacent normal tissues and normal prostate cells, respectively...
June 2018: Cancer Biotherapy & Radiopharmaceuticals
Laurel Grant, Shantanu Banerji, Leigh Murphy, David E Dawe, Craig Harlos, Yvonne Myal, Zoann Nugent, Anne Blanchard, Carla R Penner, Gefei Qing, Marshall W Pitz
Lung cancer is the most common cause of cancer-related deaths worldwide with non-small cell lung cancer (NSCLC) making up most of these cases. Males have poorer overall survival compared to women following a lung cancer diagnosis. Many studies have focused on the effects of estrogen to explain higher survival rates among women, but few have looked at the effects of androgens. We describe the expression of the androgen receptor (AR) and Ki67 in lung cancer specimens in the Manitoba Tumor Bank (MTB) and correlate these factors with patient outcome...
June 18, 2018: Hormones & Cancer
Y Wang, Y Wei, X Tang, B Liu, L Shen, C Long, T Lin, D He, S Wu, G Wei
INTRODUCTION: Previous studies have revealed the relationship between androgen receptor (AR) CAG and/or GGC polymorphisms and risk of cryptorchidism, yet the results have been elusive and controversial. AIM: To determine whether AR polymorphic CAG and/or GGC repeats are related to cryptorchidism. STUDY DESIGN: The relevant studies were obtained from PubMed, Embase, China National Knowledge Infrastructure, and Wanfang. The pooled odds ratios with 95% confidence intervals (CIs) were used to assess the strength of associations...
June 7, 2018: Journal of Pediatric Urology
Joel Wahl, Martin Smieško
The androgen receptor (AR) is a key target for the development of drugs targeting hormone-dependent prostate cancer, but has also an important role in endocrine disruption. Reliable prediction of the binding of ligands towards the AR is therefore of great relevance. Molecular docking is a powerful computational method for exploring small-ligand binding to proteins. It can be applied for virtual screening experiments but also for predicting molecular initiating events in toxicology. However, in case of AR, there is no antagonist-bound crystal structure yet available...
June 15, 2018: International Journal of Molecular Sciences
Reyna Cristina Colli-Dula, Xiefan Fang, David Moraga-Amador, Nacira Albornoz-Abud, Roberto Zamora-Bustillos, Ana Conesa, Omar Zapata-Perez, Diego Moreno, Emanuel Hernandez-Nuñez
Despite a wide number of toxicological studies that describe benzo[a]pyrene (BaP) effects, the metabolic mechanisms that underlie these effects in fish are largely unknown. Of great concern is the presence of BaP in aquatic systems, especially those in close proximity to human activity leading to consumption of potentially contaminated foods. BaP is a known carcinogen and it has been reported to have adverse effects on the survival, development and reproduction of fish. The purpose of this study was to investigate if a low dose of BaP can alter genes and key metabolic pathways in the liver and testis in male adult tilapia, and whether these could be associated with biological endpoints disruption...
June 8, 2018: Aquatic Toxicology
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