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Ishfaq A Sheikh, Iftikhar A Tayubi, Ejaz Ahmad, Majid A Ganaie, Osama S Bajouh, Samera F AlBasri, Ibtihal M J Abdulkarim, Mohd A Beg
Environmental contamination has been one of the major drawbacks of the industrial revolution. Several man-made chemicals are constantly released into the environment during the manufacturing process and by leaching from the industrial products. As a result, human and animal populations are exposed to these synthetic chemicals on a regular basis. Many of these chemicals have adverse effects on the physiological functions, particularly on the hormone systems in human and animals and are called endocrine disrupting chemicals (EDCs)...
October 14, 2016: Ecotoxicology and Environmental Safety
Maria Magdalena Montt-Guevara, Jorge Eduardo Shortrede, Maria Silvia Giretti, Andrea Giannini, Paolo Mannella, Eleonora Russo, Alessandro David Genazzani, Tommaso Simoncini
The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgen receptor (AR) is expressed in approximately 70 to 90% of invasive breast carcinomas, which has prognostic relevance in basal-like cancers and in triple-negative breast cancers. Recent studies have associated the actin-binding proteins of the ezrin-radixin-moesin (ERM) family with metastasis in endocrine-sensitive cancers. We studied on T47D breast cancer cells whether androgens with different characteristics, such as testosterone (T), dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA) may regulate breast cancer cell motility and invasion through the control of actin remodeling...
2016: Frontiers in Endocrinology
Katherine E Joyce, Mary L Biggs, Luc Djoussé, Joachim H Ix, Jorge R Kizer, David S Siscovick, Molly M Shores, Alvin M Matsumoto, Kenneth J Mukamal
CONTEXT: Although sex hormone binding globulin (SHBG) and testosterone (T) have been inversely associated with risk of diabetes, few studies have examined dihydrotestosterone (DHT), a more potent androgen than T, or older adults, whose glycemic pathophysiology differs from younger adults. OBJECTIVE: To determine the associations of SHBG, T, and DHT with insulin resistance and incident diabetes in older adult men. DESIGN: In a prospective cohort study, we evaluated baseline levels of SHBG, T, and DHT using liquid chromatography-tandem mass spectrometry among 852 men in the Cardiovascular Health Study free of diabetes and cardiovascular disease in 1994...
October 12, 2016: Journal of Clinical Endocrinology and Metabolism
Hye-Eun Choi, Ji-Sun Shin, Dong-Gyu Leem, Soo-Dong Kim, Won-Jea Cho, Kyung-Tae Lee
Previously, we reported that 6-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(6-methylpyridin-2-yl) nicotinamide (DIMN) analogues inhibited the growth of prostate cancer cells as an anti-androgenic compound. In the present study, we evaluated cytotoxic effects of these DIMN derivatives and found that DIMN-26 most potently inhibited the proliferation of the LNCap-LN3 androgen-dependent and DU145 androgen-independent prostate cancer cells through induction of G2/M phase cell cycle arrest and subsequent apoptosis. The G2/M phase arrest was found due to increases in the activation of cdc2 (also known as cyclin-dependent kinase 1, CDK1)/cyclin B1 complex...
October 5, 2016: Chemico-biological Interactions
Ishfaq A Sheikh, Muhammad Yasir, Muhammad Abu-Elmagd, Tanveer A Dar, Adel M Abuzenadah, Ghazi A Damanhouri, Mohammed Al-Qahtani, Mohd A Beg
BACKGROUND: Currently, alternate plasticizers are used to replace phthalate plasticizers in children's toys, medical equipments and food packaging, due to the adverse effects of phthalate compounds on human health and laws prohibiting their use. Current information regarding the safety and potential adverse effects of alternate plasticizers is limited and recent studies have found alternate plasticizers to display similar characteristics to those observed in phthalate plasticizers. This study was undertaken to evaluate and predict the potential endocrine disrupting activity of the three most commonly used alternate plasticizers: di(2-ethylhexyl)terephthalate (DEHT), tris(2-ethylhexyl)trimellitate (TOTM), and diisononyl hexahydrophthalate (DINCH) against human sex hormone-binding globulin (SHBG) using in silico approaches...
September 30, 2016: BMC Structural Biology
Emily J Faivre, Denise Wilcox, Xiaoyu Lin, Paul Hessler, Maricel Torrent, Wei He, Tamar Uziel, Daniel H Albert, Keith McDaniel, Warren Kati, Yu Shen
: Competitive inhibitors of acetyl-lysine binding to the bromodomains of the BET (bromodomain and extra terminal) family are being developed for the treatment of solid and hematologic malignancies. The function of BET family member BRD4 at enhancers/super-enhancers has been shown to sustain signal-dependent or pathogenic gene expression programs. Here the hypothesis was tested that the transcription factor drivers of castration-resistant prostate cancer (CRPC) clinical progression, including the Androgen Receptor (AR), are critically dependent on BRD4 and thus represent a sensitive solid tumor indication for the BET inhibitor ABBV-075...
October 5, 2016: Molecular Cancer Research: MCR
Nagarajarao Shamaladevi, Shinako Araki, Dominic A Lyn, Rajnikanth Ayyathurai, Jie Gao, Vinata B Lokeshwar, Hugo Navarrete, Bal L Lokeshwar
BIRM is an anticancer herbal formulation from Ecuador. Previous study established its antitumor and antimetastatic activity against prostate cancer models. The activity of BIRM against human prostate cancer (PCa) cells was investigated to uncover its mechanism of antitumor activity. In androgen receptor (AR)-expressing PCa cells BIRM was 2.5-fold (250%) more cytotoxic in presence of androgen (DHT) compared to cells grown in the absence of DHT. In AR-positive cells (LAPC-4 and LNCaP) BIRM caused a dose and time-dependent down-regulation of AR and increased apoptosis...
October 1, 2016: Oncotarget
Ronda F Greaves, Lisa Jolly, Michaela F Hartmann, Chung Shun Ho, Richard K T Kam, John Joseph, Conchita Boyder, Stefan A Wudy
BACKGROUND: Serum dihydrotestosterone (DHT) is an important analyte for the clinical assessment of disorders of sex development. It is also reportedly a difficult analyte to measure. Currently, there are significant gaps in the standardisation of this analyte, including no external quality assurance (EQA) program available worldwide to allow for peer review performance of DHT. We therefore proposed to establish a pilot EQA program for serum DHT. METHODS: DHT was assessed in the 2015 Royal College of Pathologists of Australasia Quality Assurance Programs' Endocrine program material...
October 4, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
H Suzuki, S Matsushita, K Suzuki, G Yamada
Androgen is an essential factor involved in masculinization of external genitalia. Failure of the exposure to 5α-dihydrotestosterone (DHT) causes a hypoplastic penile size and urethral abnormality. The main pathology of hypospadias is defective urethral closure on the ventral side of the penis. Hormone-dependent genes are suggested as the causative factors. However, the detailed mechanisms of DHT functions on urethral tube formation remain unknown. Androgen is both a positive and negative regulator of cell proliferation...
October 1, 2016: Andrology
Verónica Torres-Estay, Daniela V Carreño, Patricia Fuenzalida, Anica Watts, Ignacio F San Francisco, Viviana P Montecinos, Paula C Sotomayor, John Ebos, Gary J Smith, Alejandro S Godoy
BACKGROUND: Sex-related differences in the role of androgen have been reported in cardiovascular diseases and angiogenesis. Moreover, androgen receptor (AR) has been causally involved in the homeostasis of human prostate endothelial cells. However, levels of expression, functionality and biological role of AR in male- and female-derived human endothelial cells (ECs) remain poorly characterized. The objectives of this work were (1) to characterize the functional expression of AR in male- and female-derived human umbilical vein endothelial cell (HUVEC), and (2) to specifically analyze the biological effects of DHT, and the role of AR on these effects, in male-derived HUVECs (mHUVECs)...
September 27, 2016: Angiogenesis
Shehzad Basaria, Ravi Jasuja, Grace Huang, Whitney Wharton, Hong Pan, Karol Pencina, Zhuoying Li, Thomas G Travison, Jag Bhawan, Renaud Gonthier, Fernand Labrie, Alain Y Dury, Carlo Serra, Allen Papazian, Michael O'Leary, Sami Amr, Thomas W Storer, Emily Stern, Shalender Bhasin
CONTEXT: Some men who use finasteride for hair loss report persistent sexual and other symptoms after discontinuing finasteride therapy. OBJECTIVE: To determine whether these persistent symptoms after discontinuation of finasteride use are due to androgen deficiency, decreased peripheral androgen action, or persistent inhibition of steroid 5α-reductase (SRD5A) enzymes. PARTICIPANTS: Finasteride-users, who reported persistent sexual symptoms after discontinuing finasteride (group 1); age-matched finasteride-users who did not report sexual symptoms (group 2); and healthy men who had never used finasteride (group 3)...
September 23, 2016: Journal of Clinical Endocrinology and Metabolism
Michaël R Laurent, Ferran Jardí, Vanessa Dubois, Dieter Schollaert, Rougin Khalil, Evelien Gielen, Geert Carmeliet, Frank Claessens, Dirk Vanderschueren
Aging hypogonadal men are at increased risk of osteoporosis and sarcopenia. Testosterone is a potentially appealing strategy to prevent simultaneous bone and muscle loss. The androgen receptor (AR) mediates antiresorptive effects on trabecular bone via osteoblast-lineage cells, as well as muscle-anabolic actions. Sex steroids also modify the skeletal response to mechanical loading. However, it is unclear whether the effects of androgens on bone remain effective independent of mechanical stimulation or rather require indirect androgen effects via muscle...
September 10, 2016: Bone
Wensen Pan, Shuo Han, Lin Kang, Sha Li, Juan Du, Huixian Cui
The current study focused on how dihydrotestosterone (DHT) regulates synaptic plasticity in the hippocampus of mild cognitive impairment male senescence-accelerated mouse prone 8 (SAMP8) mice. Five-month-old SAMP8 mice were divided into the control, castrated and castrated-DHT groups, in which the mice were castrated and treated with physiological doses of DHT for a period of 2 months. To determine the regulatory mechanisms of DHT in the cognitive capacity, the effects of DHT on the morphology of the synapse and the expression of synaptic marker proteins in the hippocampus were investigated using immunohistochemistry, qPCR and western blot analysis...
September 2016: Experimental and Therapeutic Medicine
John J Stocking, Michael V Fiandalo, Elena A Pop, John H Wilton, Gissou Azabdaftari, James L Mohler
BACKGROUND: Eunuchs rarely, if ever, develop prostate cancer (CaP). This article reports on a 62-year-old functional eunuch from prepubertal mumps orchitis who developed clinically localized CaP. METHODS: Serum and CaP and benign prostate tissue androgen levels were measured using a validated liquid chromatography-tandem mass spectrometry assay. The assay measures testosterone; dihydrotestosterone (DHT); the adrenal androgens, androstenedione and dehydroepiandrosterone; and the androgen metabolites, androsterone and androstanedione...
September 2016: Journal of the National Comprehensive Cancer Network: JNCCN
N C Hornig, M Ukat, H U Schweikert, O Hiort, R Werner, S L S Drop, M Cools, I A Hughes, L Audi, S F Ahmed, J Demiri, P Rodens, L Worch, G Wehner, A E Kulle, D Dunstheimer, E Müller-Roßberg, T Reinehr, A T Hadidi, A K Eckstein, C van der Horst, C Seif, R Siebert, O Ammerpohl, P-M Holterhus
CONTEXT: Only about 85% of patients with clinical diagnosis complete androgen insensitivity syndrome (CAIS) and less than 30% with partial androgen insensitivity syndrome (PAIS) can be explained by inactivating mutations in the androgen receptor (AR) gene. OBJECTIVE: To clarify this discrepancy by in-vitro determination of AR transcriptional activity in individuals with disorders of sex development (DSD) and male controls. DESIGN: Quantification of dihydrotestosterone (DHT)-dependent transcriptional induction of the AR target gene apolipoprotein D (APOD) in cultured genital fibroblasts (GF) (APOD-assay) and next generation sequencing (NGS) of the complete coding - and non-coding AR-locus...
September 1, 2016: Journal of Clinical Endocrinology and Metabolism
Antje Schröder, Daniel B Abrar, Ulrike Hampel, Martin Schicht, Friedrich Paulsen, Fabian Garreis
Meibomian gland dysfunction (MGD) is considered the most common cause of dry eye disease (DED). Sex hormones seem to play a role in the pathogenesis of MGD although their involvement is not completely understood. Therefore, in the present study we evaluated the effect of dihydrotestosteron (DHT) and estradiol (β-Est) on an immortalized human meibomian gland epithelial cell line (HMGEC). Protein expression of sex hormone receptors in HMGEC was investigated by western blot. Ultrastructural morphology, Sudan III lipid staining, cell proliferation as well as vitality assays were performed...
October 2016: Experimental Eye Research
Nicholas C D'Amato, Michael A Gordon, Beatrice Babbs, Nicole S Spoelstra, Kiel T Carson Butterfield, Kathleen C Torkko, Vernon T Phan, Valerie N Barton, Thomas J Rogers, Carol A Sartorius, Anthony Elias, Jason Gertz, Britta M Jacobsen, Jennifer K Richer
: Androgen receptor (AR) is expressed in 90% of estrogen receptor alpha positive (ER+) breast tumors, but its role in tumor growth and progression remains controversial. Use of two anti-androgens that inhibit AR nuclear localization, enzalutamide and MJC13, revealed that AR is required for maximum ER genomic binding. Here, a novel global examination of AR chromatin binding found that estradiol induced AR binding at unique sites compared to dihydrotestosterone (DHT). Estradiol-induced AR binding sites were enriched for estrogen response elements and had significant overlap with ER binding sites...
August 26, 2016: Molecular Cancer Research: MCR
Takashi Ando, Tsutomu Nishiyama, Itsuhiro Takizawa, Fumio Ishizaki, Yoshimichi Miyashiro, Keisuke Takeda, Noboru Hara, Yoshihiko Tomita
Intratumoural dihydrotestosterone (DHT) synthesis could be an explanation for castration resistance in prostate cancer (PC). By using liquid chromatography-mass spectrometry, we evaluated the intratumoral DHT synthesis from 5α-androstane-3β,17β-diol (3β-diol), which is inactive androgen metabolized from DHT. 3β-diol had biochemical potential to be converted to DHT via three metabolic pathways and could stimulate PC cell growth. Especially, 3β-diol was not only converted back to upstream androgens such as dehydroepiandrosterone (DHEA) or Δ5-androstenediol but also converted directly to DHT which is the main pathway from 3β-diol to DHT...
2016: Scientific Reports
Xuechao Wan, Wenhua Huang, Shu Yang, Yalong Zhang, Honglei Pu, Fangqiu Fu, Yan Huang, Hai Wu, Tao Li, Yao Li
Prostate cancer (PCa) is a leading cause of mortality among males. Long non-coding RNAs (lncRNAs) are subclass of noncoding RNAs that may act as biomarkers and therapeutic targets. In this study, we firstly conducted analysis of global lncRNA expression patterns by using our own cohort (GSE73397) and two public available gene expression datasets: The Cancer Genome Atlas (TCGA) and GSE55909. Next, we performed microarray to observe genome-wide lncRNAs' expressions under dihydrotestosterone (DHT) stimulation in LNCaP cells (GSE72866), and overlapped the result with ChIPBase data to predict androgen-responsive lncRNAs with ARE...
August 19, 2016: Oncotarget
Anna Herman, Andrzej P Herman
This article discusses the mechanisms via topically applied products containing herbs and their active constituents affect the hair growth process. It was reported that the mechanisms involving (1) insulin-like growth factor-I (IGF-I), (2) vascular endothelial growth factor (VEGF), (3) epidermal growth factor (EGF), (4) fibroblast growth factor 2 (FGF-2), (5) endothelial nitric oxide synthase (eNOS), (6) Wnt/β-catenin signalling pathway, (7) prostaglandin E (PGE), (8) prostaglandin F (PGF) stimulate hair growth, whereas the mechanisms engaging (1) 5α-reductase and dihydrotestosterone (DHT), (2) transforming growth factor beta (TGF-β), (3) fibroblast growth factor 5 (FGF-5), (4) prostaglandin D2 (PGD2) inhibit hair growth...
October 2016: Fitoterapia
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