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Michael V Fiandalo, John J Stocking, Elena A Pop, John H Wilton, Krystin M Mantione, Yun Li, Kristopher M Attwood, Gissou Azabdaftari, Yue Wu, David S Watt, Elizabeth M Wilson, James L Mohler
Androgen deprivation therapy (ADT) is palliative and prostate cancer (CaP) recurs as lethal castration-recurrent/resistant CaP (CRPC). One mechanism that provides CaP resistance to ADT is primary backdoor androgen metabolism, which uses up to four 3α-oxidoreductases to convert 5α-androstane-3α,17β-diol (DIOL) to dihydrotestosterone (DHT). The goal was to determine whether inhibition of 3α-oxidoreductase activity decreased conversion of DIOL to DHT. Protein sequence analysis showed that the four 3α-oxidoreductases have identical catalytic amino acid residues...
February 16, 2018: Oncotarget
Tong Sun, Shin-Yi Du, Joshua Armenia, Fangfang Qu, Jingyu Fan, Xiaodong Wang, Teng Fei, Kazumasa Komura, Shirley X Liu, Gwo-Shu Mary Lee, Philip W Kantoff
Mechanisms by which non-coding RNAs contribute to the progression of hormone-sensitive prostate cancer (PCa) (HSPC) to castration-resistant PCa (CRPC) remain largely unknown. We previously showed that microRNA-221/222 is up-regulated in CRPC and plays a critical role in modulating androgen receptor function during CRPC development. With further investigation, we characterized a putative promoter region located 23.3 kb upstream of the miR-221/222 gene, and this promoter is differentially activated in CRPC LNCaP-Abl cells, leading to the up-regulation of miR-221/222...
March 13, 2018: Oncogenesis
Lucía Isidoro, Mercedes Ferrer, Mercedes Perusquía
BACKGROUND: Testosterone, 5α- and 5β-dihydrotestosterone (-DHT) induce an acute in vitro vasorelaxation and in vivo vasodepressor, hypotensive and antihypertensive responses. Our aim was to study whether androgen-induced blood pressure (BP) reduction is involved with a blockade of Ca2+ influx through L-type voltage-operated calcium channels (L-VOCCs) and/or the signaling pathways of α1 -adrenoceptors to induce vasoconstriction, which are one of the major mechanisms of BP maintenance...
March 12, 2018: Endocrine Research
Zihong He, Tuomo Rankinen, Arthur S Leon, James S Skinner, André Tchernof, Claude Bouchard
BACKGROUND/OBJECTIVES: Plasma steroid hormone levels vary between men and women, but their associations with BMI and adiposity are controversial. Furthermore, little is known about the role of exercise programs on the relationship between steroid hormones and adiposity. This report evaluates these relationships for plasma levels of adrenal, gonadal, and conjugated steroids with body composition and fat distribution in sedentary men and women, aged 17-65 years, and their responses to an exercise program...
March 5, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Yanling Guo, Xiaxia Wu, Qin Wu, Yuanfu Lu, Jingshan Shi, Xiuping Chen
Ulcerative colitis (UC) is a chronic and relapsing inflammatory disorder of the colon and rectum with increasing morbidity in recent years. 15,16-dihydrotanshinone Ӏ (DHT) is a natural product with multiple bioactivities. In this study, we aimed to investigate the protective effect and potential mechanisms of DHT on UC. Dextran sulfate sodium salt (DSS) was administrated in drinking water for 7 days to induce UC in mice. DHT (10 and 25 mg/kg) significantly alleviated DSS-induced body weight loss, disease activity index (DAI) scores, and improved histological alterations of colon tissues...
February 26, 2018: Toxicology and Applied Pharmacology
Tomofumi Yatsu, Taichi Kusakabe, Keisuke Kato, Yoshio Inouye, Kiyomitsu Nemoto, Yuichiro Kanno
Androgens are key regulators that play a critical role in the male reproductive system and have anabolic effects on bone mineral density and skeletal muscle mass. We have previously reported that YK11 is a novel selective androgen receptor modulator (SARM) and induces myogenic differentiation and selective gene regulation. In this study, we show that treatment of YK11 and dihydrotestosterone (DHT) accelerated cell proliferation and mineralization in MC3T3-E1 mouse osteoblast cells. Further, YK11-treated cells increased osteoblast specific differentiation markers, such as osteoprotegerin and osteocalcin, compared to untreated cells...
2018: Biological & Pharmaceutical Bulletin
Bhakti R Pathak, Ananya A Breed, Priyanka Deshmukh, Smita D Mahale
Cysteine-rich secretory protein 3 (CRISP3) is one of the most upregulated genes in prostate cancer. Androgen receptor (AR) plays an important role not only in initial stages of prostate cancer development but also in the advanced stage of castration-resistant prostate cancer (CRPC). Role of AR in regulation of CRISP3 expression is not yet known. In order to understand the regulation of CRISP3 expression, various overlapping fragments of CRISP3 promoter were cloned in pGL3 luciferase reporter vector. All constructs were transiently and stably transfected in PC3 (CRISP3 negative) and LNCaP (CRISP3 positive) cell lines and promoter activity was measured by luciferase assay...
February 22, 2018: Journal of Steroid Biochemistry and Molecular Biology
Yueh-Ming Tai, Chih-Yuan Ko, Chen-Cheng Lin, Yu-Yue Wan, Jing-Yi Chung, Yia-Ping Liu
OBJECTIVE: Central 5-HT1A receptor is involved in the modulation of sensorimotor gating function. However, its precise role is not clearly defined in developmentally social deprived (isolation rearing, IR) rats featured with impaired sensorimotor gating ability. We therefore aimed to examine the effects of 5HT1A activation on acoustic startle response (ASR) and prepulse inhibition (PPI) in IR rats in a condition of compromised presynaptic 5-HT functions. METHODS: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletor, 5,7-DHT...
February 2018: Psychiatry Investigation
Fanxing Zeng, Hua Zhao, Jingwen Liao
This study was designed to investigate the effects of exogenous androgen and resistance exercise on skeletal muscle hypertrophy and the role of the mammalian target of rapamycin (mTOR) signalling during the process. A total of 24 male Sprague-Dawley rats were randomly assigned to sham operation and dihydrotestosterone (DHT) implantation groups with subgroups subjected to sedentary conditions or resistance exercise (SHAM+SED, SHAM+EX, DHT+SED, and DHT+EX). The experimental procedure lasted for 10 days. The mRNA expression of androgen receptor (AR) and insulin-like growth factor I (IGF-I), the expression of myosin heavy chain (MHC), as well as the phosphorylation statuses of AR, mTOR, p70 ribosomal S6 kinase (p70S6K ), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) were determined in the white gastrocnemius muscle...
December 2017: Biology of Sport
Yi X Chan, Bu B Yeap
PURPOSE OF REVIEW: Androgens have been implicated in prostate growth; however, the role of androgens in prostate cancer development is not clear. Furthermore, studies suggest a role for androgens in female-hormone-dependent cancers and common nonhormone dependent cancers. This study aims to review key studies and more recent studies of dihydrotestosterone (DHT) and cancer risk. RECENT FINDINGS: Epidemiological studies are reassuring as they have not associated endogenous androgens with prostate cancer risk...
February 19, 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
Inês Margarida Gomes, Sandra Moreira Rocha, Carlos Gaspar, Maria Inês Alvelos, Cecília Reis Santos, Sílvia Socorro, Cláudio Jorge Maia
Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is overexpressed in numerous types of tumors, especially in prostate cancer. STEAP1 is located in the plasma membrane of epithelial cells and may play an important role in inter- and intracellular communication. Several studies suggest STEAP1 as a potential biomarker and an immunotherapeutic target for prostate cancer. However, the role of STEAP1 in cell proliferation and apoptosis remains unclear. Therefore, the role of STEAP1 in prostate cancer cells proliferation and apoptosis was determined by inducing STEAP1 gene knockdown in LNCaP cells...
February 20, 2018: Medical Oncology
Amit Sethi, Lingdao Sha, Neeraj Kumar, Virgilia Macias, Ryan J Deaton, Peter H Gann
OBJECTIVE: To determine whether a computer vision-based approach applied to H&E prostate biopsy images can distinguish dutasteride-treated tissue from placebo, and identify features associated with degree of responsiveness to 5α-reductase inhibitor (5ARI) therapy. SUBJECTS AND METHODS: Our study population comprised 100 treatment-compliant men without prostate cancer assigned to dutasteride or placebo in the REDUCE trial who had slides available from mandatory Year 4 biopsies...
February 20, 2018: BJU International
Takako Kawanami, Tomoko Tanaka, Yuriko Hamaguchi, Takashi Nomiyama, Hajime Nawata, Tosihiko Yanase
We previously identified a novel selective androgen receptor modulator (SARM), S42, which does not stimulate prostate growth but has a beneficial effect on lipid metabolism. In the prostate cancer (PC) cell line LNCaP, S42 did not induce androgen receptor (AR) transactivation but antagonized 5α-dihydrotestosterone (DHT)-induced AR activation. Next, we investigated whether S42 suppresses the growth of PC cell lines. Basal growth of LNCaP cells was significantly suppressed by treatment with S42 compared with vehicle, as determined by cell counting and BrdU assays...
February 12, 2018: Endocrinology
Riikka Oksala, Anu Moilanen, Reetta Riikonen, Petteri Rummakko, Arja Karjalainen, Mikko Passiniemi, Gerd Wohlfahrt, Päivi Taavitsainen, Chira Malmström, Meri Ramela, Hanna-Maija Metsänkylä, Riikka Huhtaniemi, Pekka J Kallio, Mika Vj Mustonen
We report the discovery of a novel nonsteroidal dual-action compound, ODM-204, that holds promise for treating patients with castration-resistant prostate cancer (CRPC), an advanced form of prostate cancer characterised by high androgen receptor (AR) expression and persistent activation of the AR signaling axis by residual tissue androgens. For ODM-204, has a dual mechanism of action. The compound is anticipated to efficiently dampen androgenic stimuli in the body by inhibiting CYP17A1, the prerequisite enzyme for the formation of dihydrotestosterone (DHT) and testosterone (T), and by blocking AR with high affinity and specificity...
February 10, 2018: Journal of Steroid Biochemistry and Molecular Biology
Edwin D Lephart
Estrogens are known to have protective and favorable influences on skin health; conversely, androgens oppose the actions of estrogens. Estrogen's chemical messages are transmitted via the classical nuclear hormone estrogen receptors (ER) alpha and beta and the rapid-acting G-coupled membrane estrogen receptor. Androgens [both testosterone and 5α-dihydrotestosterone (5α-DHT)] bind the same androgen receptor. Estrogen levels peak in the mid- to late 20s in women and then decline by 50% by 50 years of age and dramatically decrease further after menopause...
February 13, 2018: Journal of Cosmetic Dermatology
Angélique Quartier, Laure Chatrousse, Claire Redin, Céline Keime, Nicolas Haumesser, Anne Maglott-Roth, Laurent Brino, Stéphanie Le Gras, Alexandra Benchoua, Jean-Louis Mandel, Amélie Piton
BACKGROUND: Prenatal exposure to androgens during brain development in male individuals may participate to increase their susceptibility to develop neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability. However, little is known about the action of androgens in human neural cells. METHODS: We used human neural stem cells differentiated from embryonic stem cells to investigate targets of androgens. RESULTS: RNA sequencing revealed that treatment with dihydrotestosterone (DHT) leads to subtle but significant changes in the expression of about 200 genes, encoding proteins of extracellular matrix or involved in signal transduction of growth factors (e...
January 9, 2018: Biological Psychiatry
Gaelle Rondeau, Parisa Abedinpour, Adrian Chrastina, Jennifer Pelayo, Per Borgstrom, John Welsh
Treatment of mice harboring PTEN-P2 tumors in the prostate or on prostate tissue in vivo with 5-hydroxy-2-methyl-1,4-naphthoquinone, also known as plumbagin, results in tumor regression in castrated mice, but not in intact mice. This suggested that dihydrotestosterone (DHT) production in the testes may prevent cell death due to plumbagin treatment, but the underlying mechanism is not understood. We performed RNA-seq analysis on cells treated with combinations of plumbagin and DHT, and analyzed differential gene expression, to gain insight into the interactions between androgen and plumbgin...
February 9, 2018: Scientific Reports
Wei Zhang, Xiaozhen Liu, Shan Liu, Ying Qin, Xiaoqi Tian, Fengting Niu, Han Liu, Ning Liu, Yun Niu
Androgen receptor (AR) is an important transcriptional factor, which is frequently expressed in invasive breast cancer and correlates patients' prognosis. Our previous results indicate AR activation may increase let-7a expression in breast cancer cells, while let-7, a tumor suppressor, is reported to inhibit breast tumor-initiating cells (T-IC). The study aims to explore the effects of AR/let-7a signaling on breast T-IC and its regulatory mechanism. The results revealed that the expression of AR was significantly associated with let-7a and CD44+/24-/low especially in estrogen receptor positive (ER+) breast cancer tissues...
January 9, 2018: Oncotarget
Hee-Seok Lee, Da-Woon Jung, Songyi Han, Hui-Seung Kang, Jin-Hyang Suh, Hyun-Suk Oh, Myung-Sil Hwang, Guiim Moon, Yooheon Park, Jin-Hwan Hong, Yong Eui Koo
Trenbolone acetate (TBA) is a synthetic anabolic steroidal growth factor that is used for rapid muscle development in cattle. The absorbed TBA is hydrolyzed to the active form, 17β-trenbolone (17 TB; 17β-hydroxy-estra-4,9,11-trien-3-one) in meat and milk products, which can cause adverse health effects in humans. Similar to 5α-dihydrotestosterone (DHT), 17 TB was reported to exhibit endocrine disrupting effects on animals and humans due to its androgenic effect via binding to the androgen receptor. The purpose of this study is to investigate the molecular mechanism of cell proliferation in prostate cancer (PCa) cells treated with 17 TB...
May 2018: Chemosphere
Leilei Sun, Bafang Li, Di Yao, Wenkui Song, Hu Hou
The objective of this study was to explore the effects of dehydrothermal treatment (DHT) and glutaraldehyde (GTA) cross-linking on mechanical, biological properties and biodegradation behavior of Nile tilapia skin collagen sponge fabricated by freeze-drying technology. It was found that the GTA cross-linked collagen sponge exhibited a higher degree of cross-linking in comparison with DHT. The extent of increased tensile strength as well as hygroscopicity indicated that GTA cross-linking was superior to DHT in mechanical properties and liquid absorption, which was attributed to different cross-linking mechanisms...
January 10, 2018: Journal of the Mechanical Behavior of Biomedical Materials
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