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dihydrotestosterone

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https://www.readbyqxmd.com/read/27893717/androgen-and-ar-contribute-to-breast-cancer-development-and-metastasis-an-insight-of-mechanisms
#1
J Feng, L Li, N Zhang, J Liu, L Zhang, H Gao, G Wang, Y Li, Y Zhang, X Li, D Liu, J Lu, B Huang
The role of androgen and androgen receptor (AR) in breast carcinogenesis has long been a disputed issue. This report provides a mechanistic insight into how androgen and AR contributes to invasion and metastasis of breast cancer. We find that dihydrotestosterone (DHT) is able to induce the epithelial-to-mesenchymal transition in breast cancer cells in an AR-dependent/estrogen receptor-independent manner. This process is dependent on the demethylation activity of lysine-specific demethylase 1A (LSD1) by epigenetically regulating the target genes E-cadherin and vimentin...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27893427/cholesterol-import-and-steroidogenesis-are-biosignatures-for-gastric-cancer-patient-survival
#2
Wei-Chun Chang, Shang-Fen Huang, Yang-Ming Lee, Hsueh-Chou Lai, Bi-Hua Cheng, Wei-Chung Cheng, Jason Yen-Ping Ho, Long-Bin Jeng, Wen-Lung Ma
Androgens, estrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or in vivo studies. This report used a web-based gene survival analyzer to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27890531/short-term-effects-of-diabetes-on-neurosteroidogenesis-in-the-rat-hippocampus
#3
Simone Romano, Nico Mitro, Silvia Diviccaro, Roberto Spezzano, Matteo Audano, Luis Miguel Garcia-Segura, Donatella Caruso, Roberto Cosimo Melcangi
Diabetes may induce neurophysiological and structural changes in the central nervous system (i.e., diabetic encephalopathy). We here explored whether the levels of neuroactive steroids (i.e., neuroprotective agents) in the hippocampus may be altered by short-term diabetes (i.e., one month). To this aim, by liquid chromatography-tandem mass spectrometry we observed that in the experimental model of the rat raised diabetic by streptozotocin injection, one month of pathology induced changes in the levels of several neuroactive steroids, such as pregnenolone, progesterone and its metabolites (i...
November 23, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27888135/antihypertensive-effects-of-androgens-in-conscious-spontaneously-hypertensive-rats
#4
Mercedes Perusquía, Nieves Herrera, Mercedes Ferrer, John N Stallone
Androgens are vasoactive steroids that induce acute vasodilation in a number of isolated vascular beds from different species, but the effects of these hormones on systemic blood pressure (BP) have been studied little. Although it has been reported that androgens exert systemic hypotensive effects through peripheral vasodilation in normotensive rats, there have not been any reports of systemic hypotensive effects of androgens in animals with hypertension. This study was designed to evaluate the acute effects of testosterone (TES) and its 5-reduced metabolites on systemic BP in hypertensive rats and to test the hypothesis that hypotestosteronemia may be involved in the pathogenesis of hypertension...
November 23, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27871063/dioscorea-esculenta-induced-increase-in-muscle-sex-steroid-hormones-is-associated-with-enhanced-insulin-sensitivity-in-a-type-2-diabetes-rat-model
#5
Koji Sato, Satoshi Fujita, Motoyuki Iemitsu
The effects of chronic Dioscorea esculenta administration and exercise training on muscle sex steroid hormone levels and insulin resistance in type 2 diabetes rats was assessed. Twenty-wk-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were assigned randomly to the control, D. esculenta treatment, D. esculenta with 5α-reductase inhibitor treatment, or the exercise training groups (running at 25 m/min for 1 h, 5 d/wk; n = 10 each group). Eight weeks of D. esculenta treatment or exercise training significantly attenuated the increase in plasma insulin and fasting glucose levels...
November 8, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27866534/-dihydrotestosterone-inhibits-foam-cell-formation-via-a-lectin-like-ox-low-density-lipoprotein-receptor-mediated-mechanism-in-j774-1-cell-line
#6
Y Qiu, H D Hu, B Q Hu, X Y Chen, P Y Xu, L Cui, P Li, C Liu, L Li
Objective: To investigate the effect of dihydrotestosterone (DHT) on lectin-like ox- low-density lipoprotein (LDL) receptor(LOX-1)expression and foam cell formation in the female macrophage cell line J774.1. Methods: In cultured J774.1 cells, after pretreated with DHT at concentrations of 1×10(-9) mol/L and 1×10(-8) mol/L, ox-LDL-induced LOX-1 expression and foam cell formation were investigated by quantitative real-time PCR, Western blotting, and oil-red O staining. Results: DHT at concentrations of 1×10(-9) mol/L and 1×10(-8) mol/L inhibited ox-LDL-induced LOX-1 mRNA (2...
November 15, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27857889/possible-role-of-elevated-serum-testosterone-in-pathogenesis-of-renal-stone-formation
#7
Kapil Gupta, Gurpreet Singh Gill, Rajiv Mahajan
BACKGROUND: Urolithiasis or renal stone formation occurs with three times higher frequency in males and decreases with age in parallel with the serum testosterone levels, suggesting a role played by male sex hormones. Androgens appear a promotion action and estrogens an inhibitory action on kidney stone formation in several animal models suggesting a study to be carried out to deduce the role played by serum testosterone in the formation of renal stones. AIM: The aim of this study is to define the involvement of serum total testosterone, free testosterone, and dihydrotestosterone in the pathogenesis of urolithiasis in males by comparing the results with healthy males with no present or past history of urolithiasis as controls...
October 2016: International Journal of Applied and Basic Medical Research
https://www.readbyqxmd.com/read/27849622/novel-mutations-of-the-srd5a2-and-ar-genes-in-thai-patients-with-46-xy-disorders-of-sex-development
#8
Chupong Ittiwut, Jaturong Pratuangdejkul, Vichit Supornsilchai, Sasipa Muensri, Yodporn Hiranras, Taninee Sahakitrungruang, Suttipong Watcharasindhu, Kanya Suphapeetiporn, Vorasuk Shotelersuk
BACKGROUND: Abnormalities of dihydrotestosterone conversion [5α-reductase deficiency: online Mendelian inheritance in man (OMIM) 607306] or actions of androgens [partial androgen insensitivity syndrome (PAIS): OMIM 312300] during the 8th-12th weeks of gestation cause varying degrees of undervirilized external genitalia in 46, XY disorders of sex development (DSD) with increased testosterone production. The objective of the study was to determine clinical and genetic characteristics of Thai patients with 46, XY DSD...
November 16, 2016: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/27848231/association-of-srd5a2-gene-mutations-with-risk-of-hypospadias-in-the-iranian-population
#9
M Rahimi, M Ghanbari, Z Fazeli, M Rouzrokh, S Omrani, R Mirfakhraie, M D Omrani
BACKGROUND: Hypospadias is one of the most common forms of congenital malformation of the male external genitalia worldwide. The ratio in the Iranian population is one in 250 live male births. The conversion of testosterone to dihydrotestosterone (DHT) in the presence of steroid 5α-reductase 2, which is encoded by SRD5A2 gene, plays an important role in the normal development of the male reproductive system. METHODS: We examined whether SRD5A2 gene mutations (V89L and A49T polymorphisms) are associated with the risk of hypospadias in the Iranian population...
November 15, 2016: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/27845856/modified-release-and-conventional-glucocorticoids-and-diurnal-androgen-excretion-in-congenital-adrenal-hyperplasia
#10
Christopher M Jones, Ashwini Mallappa, Nicole Reisch, Nikolaos Nikolaou, Nils Krone, Beverly A Hughes, Donna M O'Neil, Martin J Whitaker, Jeremy W Tomlinson, Karl-Heinz Storbeck, Deborah P Merke, Richard J Ross, Wiebke Arlt
CONTEXT: The classic androgen synthesis pathway proceeds via DHEA, androstenedione and testosterone to 5α-dihydrotestosterone (DHT). However, DHT synthesis can also be achieved by an alternative pathway originating from 17α-hydroxyprogesterone (17OHP), which accumulates in congenital adrenal hyperplasia (CAH). Similarly, recent work has highlighted androstenedione-derived 11-oxygenated 19-carbon steroids as active androgens and, in CAH, androstenedione is generated directly from 17OHP...
November 15, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27842977/reprint-of-steroid-5%C3%AE-reductase-2-deficiency
#11
REVIEW
Berenice B Mendonca, Rafael Loch Batista, Sorahia Domenice, Elaine M F Costa, Ivo J P Arnhold, David W Russell, Jean D Wilson
Dihydrotestosterone is a potent androgen metabolite formed from testosterone by action of 5α-reductase isoenzymes. Mutations in the type 2 isoenzyme cause a disorder of 46,XY sex development, termed 5α-reductase type 2 deficiency and that was described forty years ago. Many mutations in the encoding gene have been reported in different ethnic groups. In affected 46,XY individuals, female external genitalia are common, but Mullerian ducts regress, and the internal urogenital tract is male. Most affected males are raised as females, but virilization occurs at puberty, and male social sex develops thereafter with high frequency...
November 11, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27832095/increased-muscular-5%C3%AE-dihydrotestosterone-in-response-to-resistance-training-relates-to-skeletal-muscle-mass-and-glucose-metabolism-in-type-2-diabetic-rats
#12
Naoki Horii, Koji Sato, Noboru Mesaki, Motoyuki Iemitsu
Regular resistance exercise induces skeletal muscle hypertrophy and improvement of glycemic control in type 2 diabetes patients. Administration of dehydroepiandrosterone (DHEA), a sex steroid hormone precursor, increases 5α-dihydrotestosterone (DHT) synthesis and is associated with improvements in fasting blood glucose level and skeletal muscle hypertrophy. Therefore, the aim of this study was to investigate whether increase in muscle DHT levels, induced by chronic resistance exercise, can contribute to skeletal muscle hypertrophy and concomitant improvement of muscular glucose metabolism in type 2 diabetic rats...
2016: PloS One
https://www.readbyqxmd.com/read/27830013/dihydrotestosterone-modulates-endothelial-progenitor-cell-function-via-rhoa-rock-pathway
#13
Hao Zhang, Liang Shi, Guo-Qing Ren, Wen-Wen Sun, Yi-Bin Wang, Yi-Kun Chen, Jiang-Ning Yin, Bing Wan
BACKGROUND: Previous findings indicate that testosterone level is negatively correlated with the incidence and mortality of cardiovascular diseases in men. Endothelial progenitor cells (EPCs) play a critical role in endothelial healing and vascular integrity. This study aimed to examine the effects of dihydrotestosterone (DHT), an active metabolite of testosterone, on human EPC function and investigate the underlying mechanism. METHODS: EPCs were isolated from peripheral blood of healthy adult males and incubated with a series of concentrations (1, 10, and 100 nmol/L in dimethyl sulfoxide) of DHT for 24 h or with 10 nmol/L DHT for different periods (6, 12, 24, 36, and 48 h)...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27825431/pet-tracers-beyond-fdg-in-prostate-cancer
#14
REVIEW
David M Schuster, Cristina Nanni, Stefano Fanti
Conventional anatomical imaging with CT and MRI has limitations in the evaluation of prostate cancer. PET is a powerful imaging technique, which can be directed toward molecular targets as diverse as glucose metabolism, density of prostate-specific membrane antigen receptors, and skeletal osteoblastic activity. Although 2-deoxy-2-(18)F-FDG-PET is the mainstay of molecular imaging, FDG has limitations in typically indolent prostate cancer. Yet, there are many useful and emerging PET tracers beyond FDG, which provide added value...
November 2016: Seminars in Nuclear Medicine
https://www.readbyqxmd.com/read/27824515/tumor-inhibition-by-enzalutamide-in-a-xenograft-model-of-ovarian-cancer
#15
Brian Y Park, Rachel N Grisham, Bjørnar den Hollander, Dharmarao Thapi, Tara Berman, Elisa de Stanchina, Qin Zhou, Gopa Iyer, Carol Aghajanian, David R Spriggs
OBJECTIVES: To investigate the tumor-suppressive properties of enzalutamide in androgen-driven ovarian cancer. METHODS: Mice were implanted subcutaneously with OVCAR-3 cells and treated with dihydrotestosterone in combination with enzalutamide or vehicle control. Tumor volumes were measured twice weekly until day 56. RESULTS: Dihydrotestosterone exposure led to a significant increase in tumor growth, while concomitant treatment with enzalutamide led to significant reductions in tumor volume compared to the androgen-exposed groups...
November 25, 2016: Cancer Investigation
https://www.readbyqxmd.com/read/27824348/androgen-synthesis-in-prostate-cancer-do-all-roads-lead-to-rome
#16
REVIEW
Ryan Stuchbery, Patrick J McCoy, Christopher M Hovens, Niall M Corcoran
The accumulation of high concentrations of signalling androgens within prostate tumours that progress despite use of androgen-deprivation therapy is a clinically important mechanism of the development of castration-resistant prostate cancer. In the past 5 years, data from a number of studies have increased our understanding of the enzymes and substrates involved in intratumoural androgen biosynthesis, and have implicated three competing pathways, which are likely to account for these observations. These pathways ('canonical', 'backdoor' and '5α-dione'), which can all ultimately generate the potent signalling androgen, dihydrotestosterone, involve many of the same enzymes, but differ in terms of substrate preference, reaction sequence and the organs and tissues in which they occur...
November 8, 2016: Nature Reviews. Urology
https://www.readbyqxmd.com/read/27821559/sex-steroids-block-the-initiation-of-atherosclerosis
#17
Frederick Naftolin, Holly Mehr, Ahmed Fadiel
Atherosclerosis is the main cause of death in men and women. This so-called "hardening of the arteries" results from advanced atherogenesis, the accumulation and death of subendothelial fat-laden macrophages (vascular plaque). The macrophages are attracted as the result of signals from injured vessels recruiting and activating cells to quell the injury by inflammation. Among the recruited cells are circulating monocytes that may be captured by the formation of neural cell adhesion molecule (nCAM) tethers between the monocytes and vascular endothelium; the tethers are dependent on electrostatic binding between distal segments of apposed nCAM molecules...
December 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27813361/high-serum-dihydrotestosterone-examined-by-ultrasensitive-lc-ms-ms-as-a-predictor-of-benign-prostatic-hyperplasia-or-gleason-score-6-cancer-in-men-with-prostate-specific-antigen-levels-of-3-10%C3%A2-ng-ml
#18
Y Miyoshi, H Uemura, K Suzuki, Y Shibata, S Honma, M Harada, Y Kubota
There has been no consensus on the role of serum androgen concentrations in prostate cancer detection in men with prostate-specific antigen levels of 3-10 ng/mL. In this study, testosterone and dihydrotestosterone concentrations in blood were examined by a newly developed method using ultrasensitive liquid chromatography with two serially linked mass spectrometers (LC-MS/MS). We investigated the correlation between serum androgen levels and Gleason scores at biopsy. We analyzed data of 157 men with a total prostate-specific antigen range of 3-10 ng/mL who underwent initial systematic prostate needle biopsy for suspected prostate cancer between April 2000 and July 2003...
November 3, 2016: Andrology
https://www.readbyqxmd.com/read/27813338/dutasteride-mediated-morphological-changes-in-the-genitourinary-tract-associated-with-altered-expression-patterns-of-the-androgen-and-estrogen-receptors-in-male-rats
#19
N Enatsu, K Chiba, K Sumii, T Fukuda, K Okada, K Matsushita, M Fujisawa
We evaluated the effects of dutasteride on the genitourinary tract using fifteen 8-week-old male Sprague-Dawley rats. Animals were divided into three groups comprising five animals each and treated as follows. Group A was a control group, members of Group B received oral administration of dutasteride 0.1 mg/kg/day from the age of 8 to 16 weeks, and members of Group C were castrated at the age of 8 weeks. All rats were killed at the age of 16 weeks for the sample collection of blood, bladder, prostate, seminal vesicles, and penis...
November 3, 2016: Andrology
https://www.readbyqxmd.com/read/27801959/different-synaptic-stimulation-patterns-influence-the-local-androgenic-and-estrogenic-neurosteroid-availability-triggering-hippocampal-synaptic-plasticity-in-the-male-rat
#20
Michela Di Mauro, Alessandro Tozzi, Paolo Calabresi, Vito Enrico Pettorossi, Silvarosa Grassi
Electrophysiological recordings were used to investigate the role of the local synthesis of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) on synaptic long-term effects induced in the hippocampal CA1 region of male rat slices. Long-term depression (LTD) and long-term potentiation (LTP), induced by different stimulation patterns, were examined under the block of the DHT synthesis by finasteride, and the E2 synthesis by letrozole. We used low frequency stimulation (LFS) for LTD, high frequency stimulation (HFS) for LTP, and intermediate patterns differing in duration or frequency...
November 1, 2016: European Journal of Neuroscience
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