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https://www.readbyqxmd.com/read/28105631/association-of-genetic-variation-with-blood-pressure-traits-among-east-africans
#1
James Kayima, Jingjing Liang, Yanina Natanzon, Joaniter Nankabirwa, Isaac Ssinabulya, Jane Nakibuuka, Achilles Katamba, Harriet Mayanja-Kizza, Alexander Miron, Chun Li, Xiaofeng Zhu
Genetic variation may explain some of the disparity in prevalence and control of hypertension across sub-Saharan Africa. Twenty-seven blood pressure (BP) related single nucleotide polymorphisms (SNPs) were genotyped among 2881samples from participants in the MEPI-CVD survey. Associations with known BP variants were evaluated for SBP, DBP and PP as continuous variables and for HTN as a binary variable. Eleven SNPS were associated with at least one BP trait (P < 0.05). Four SNPs; rs2004776, rs7726475, rs11837544 and rs2681492 whose nearest genes are AGT, NPR3/SUB1, PLXNC1 and ATP2B1 respectively were associated with SBP...
January 20, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28105086/differentiation-of-human-umbilical-cord-mesenchymal-stem-cells-into-steroidogenic-cells-in-vitro
#2
Xiaoyu Xing, Zhiyuan Zhang, Liang Zhong, Guanqun Ju, Xiangyu Zou, Yingjian Zhu, Jie Sun
Although previous studies have shown that stem cells can be differentiated into Leydig cells by gene transfection, a simple, safe and effective induction method has not yet been reported. Therefore, the present study investigated novel methods for the induction of human umbilical cord mesenchymal stem cell (HUMSC) differentiation into Leydig-like, steroidogenic cells. HUMSCs were acquired using the tissue block culture attachment method, and the expression of MSC surface markers was evaluated by flow cytometry...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28089693/effects-of-six-priority-controlled-phthalate-esters-with-long-term-low-dose-integrated-exposure-on-male-reproductive-toxicity-in-rats
#3
Hai-Tao Gao, Run Xu, Wei-Xin Cao, Liang-Liang Qian, Min Wang, Lingeng Lu, Qian Xu, Shu-Qin Yu
Human beings are inevitably exposed to ubiquitous phthalate esters (PEs) surroundings. The purposes of this study were to investigate the effects of long-term low-dose exposure to the mixture of six priority controlled phthalate esters (MIXPs): dimethyl phthalate (DMP), diethyl phthalate (DEP), di(n-butyl) phthalate (DBP), butyl benzyl phthalate (BBP), di(2-ethyhexyl) phthalate (DEHP) and di-n-octyl phthalate (DNOP), on male rat reproductive system and further to explore the underlying mechanisms of the reproductive toxicity...
January 12, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28059143/influence-of-coronary-artery-disease-and-subclinical-atherosclerosis-related-polymorphisms-on-the-risk-of-atherosclerosis-in-rheumatoid-arthritis
#4
Raquel López-Mejías, Alfonso Corrales, Esther Vicente, Montserrat Robustillo-Villarino, Carlos González-Juanatey, Javier Llorca, Fernanda Genre, Sara Remuzgo-Martínez, Trinidad Dierssen-Sotos, José A Miranda-Filloy, Marco A Ramírez Huaranga, Trinitario Pina, Ricardo Blanco, Juan J Alegre-Sancho, Enrique Raya, Verónica Mijares, Begoña Ubilla, Iván Ferraz-Amaro, Carmen Gómez-Vaquero, Alejandro Balsa, Francisco J López-Longo, Patricia Carreira, Isidoro González-Álvaro, J Gonzalo Ocejo-Vinyals, Luis Rodríguez-Rodríguez, Benjamín Fernández-Gutiérrez, Santos Castañeda, Javier Martín, Miguel A González-Gay
A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2)...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28008861/delayed-diagnosis-of-a-17-hydroxylase-17-20-lyase-deficient-case-presented-with-46-xy-female-low-normal-potassium-can-alert-clinician
#5
Emine Çamtosun, Zeynep Şıklar, Serdar Ceylaner, Pınar Kocaay, Merih Berberoğlu
17-hydroxylase/17,20-lyase deficiency (17OHD) is a rare autosomal recessive defect in adrenal and gonadal steroidogenesis, causes absence of secondary sexual characteristics frequently associated with hypertension and hyperkalemia. Here we report a 46, XY case, who had normal potassium levels and without hypertension. Here we present a 2,5 years old female admitted with female external genitalia and inguinal swelling. Pathology of biopsy revealed that this gonad is a testis. Karyotype was 46, XY. She had no hypertension and no hypokalemia...
December 23, 2016: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/27959413/17%C3%AE-%C3%A2-hydroxylase-17-20%C3%A2-lyase-deficiency-in-congenital-adrenal-hyperplasia-a-case-report
#6
Simiao Xu, Shuhong Hu, Xuefeng Yu, Muxun Zhang, Yan Yang
Congenital adrenal hyperplasia (CAH) is a rare autosomal recessive disorder caused by mutations in the cytochrome P450 family 17 subfamily A member 1 (CYP17A1) gene located on chromosome 10q24.3, which leads to a deficiency in 17α‑hydroxylase/17,20‑lyase. The disorder is characterized by low blood levels of estrogens, androgens and cortisol, which leads to a compensatory increase in adrenocorticotropic hormone levels that stimulate the production of mineralocorticoid precursors. This subsequently leads to hypertension, hypokalemia, primary amenorrhea and sexual infantilism...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27871977/a-time-course-regulatory-and-kinetic-expression-study-of-steroid-metabolizing-enzymes-by-calcitriol-in-primary-cultured-human-placental-cells
#7
Nancy Noyola-Martínez, Ali Halhali, Verónica Zaga-Clavellina, Andrea Olmos-Ortiz, Fernando Larrea, David Barrera
1,25-dihydroxivitamin D3 (calcitriol), is a secoesteroid involved in several placental functions. In particular, we and others showed that calcitriol regulates peptides, proteins, cytokines and hormones production in human trophoblastic cells. On the other hand, calcitriol modifies the activity and expression of some steroidogenic enzymes, a process that is considered tissue-specific. However, the effects of calcitriol on the expression of enzymes involved in the synthesis of sex steroids in placental tissue have not yet been entirely studied...
November 18, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27798284/assessment-of-growth-and-metabolism-characteristics-in-offspring-of-dehydroepiandrosterone-induced-polycystic-ovary-syndrome-adults
#8
Ying Huang, Jiang-Man Gao, Chun-Mei Zhang, Hong-Cui Zhao, Yue Zhao, Rong Li, Yang Yu, Jie Qiao
Polycystic ovary syndrome (PCOS) is a common reproductive disorder that has many characteristic features including hyperandrogenemia, insulin resistance and obesity, which may have significant implications for pregnancy outcomes and long-term health of women. Daughters born to PCOS mothers constitute a high-risk group for metabolic and reproductive derangements, but no report has described potential growth and metabolic risk factors for such female offspring. Hence, we used a mouse model of dehydroepiandrosterone (DHEA)-induced PCOS to study the mechanisms underlying the pathology of PCOS by investigating the growth, developmental characteristics, metabolic indexes and expression profiles of key genes of offspring born to the models...
December 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27794047/inhibition-of-akr1c3-activation-overcomes-resistance-to-abiraterone-in-advanced-prostate-cancer
#9
Chengfei Liu, Cameron M Armstrong, Wei Lou, Alan Lombard, Christopher P Evans, Allen C Gao
Abiraterone suppresses intracrine androgen synthesis via inhibition of CYP17A1. However, clinical evidence suggests that androgen synthesis is not fully inhibited by abiraterone and the sustained androgen production may lead to disease relapse. In the present study, we identified AKR1C3, an important enzyme in the steroidogenesis pathway, as a critical mechanism driving resistance to abiraterone through increasing intracrine androgen synthesis and enhancing androgen signaling. We found that overexpression of AKR1C3 confers resistance to abiraterone while downregulation of AKR1C3 resensitizes resistant cells to abiraterone treatment...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27793677/disordered-zonal-and-cellular-cyp11b2-enzyme-expression-in-familial-hyperaldosteronism-type-3
#10
Celso E Gomez-Sanchez, Xin Qi, Elise P Gomez-Sanchez, Hironobu Sasano, Martin O Bohlen, Max Wisgerhof
Three forms of familial primary aldosteronism have been recognized. Familial Hyperaldosteronism type 1 (FH1) or dexamethasone suppressible hyperaldosteronism, FH2, the most common form of as yet unknown cause(s), and FH3. FH3 is due to activating mutations of the potassium channel gene KCNJ5 that increase constitutive and angiotensin II-induced aldosterone synthesis. In this study we examined the cellular distribution of CYP11B2, CYP11B1, CYP17A1 and KCNJ5 in adrenals from two FH3 siblings using immunohistochemistry and immunofluorescence and obtained unexpected results...
January 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27775788/local-bone-marrow-renin-angiotensin-system-in-the-genesis-of-leukemia-and-other-malignancies
#11
I C Haznedaroglu, U Y Malkan
The existence of a local renin-angiotensin system (RAS) specific to the hematopoietic bone marrow (BM) microenvironment had been proposed two decades ago. Most of the RAS molecules including ACE, ACE2, AGT, AGTR1, AGTR2, AKR1C4, AKR1D1, ANPEP, ATP6AP2, CMA1, CPA3, CTSA, CTSD, CTSG, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, DPP3, EGFR, ENPEP, GPER, HSD11B1, HSD11B2, IGF2R, KLK1, LNPEP, MAS1, MME, NR3C1, NR3C2, PREP, REN, RNPEP, and THOP1 are locally present in the BM microenvironment. Local BM RAS peptides control the hematopoietic niche, myelopoiesis, erythropoiesis, thrombopoiesis and the development of other cellular lineages...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27760586/effects-of-angiogenin-on-granulosa-and-theca-cell-function-in-cattle
#12
J L Dentis, N B Schreiber, A M Burress, L J Spicer
Angiogenin is a member of the ribonuclease A superfamily of proteins that has been implicated in stimulating angiogenesis but whether angiogenin can directly affect ovarian granulosa or theca cell function is unknown. Therefore, the objective of these studies was to determine the effect of angiogenin on proliferation and steroidogenesis of bovine granulosa and theca cells. In experiments 1 and 2, granulosa cells from small (1 to 5 mm diameter) follicles and theca cells from large (8 to 22 mm diameter) follicles were cultured to evaluate the dose-response effect of recombinant human angiogenin on steroidogenesis...
October 20, 2016: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/27754305/lbos-02-06-histopathological-specific-mutation-spectrum-of-aldosterone-producing-adenomas
#13
Elena Azizan, Norlela Sukor, Nor Azmi Kamaruddin, A Rahman A Jamal, Jiri Ceral, Miroslav Solar, Isa Mohamed Rose, Geok Chin Tan
OBJECTIVE: Aldosterone-producing adenoma (APA) is a common curable cause of hypertension. Somatic mutations in five genes (KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1) have been found to cause the excess aldosterone production of two thirds of APAs [1-4]. KCNJ5 mutant APAs, the most common and largest, had explicit genotype-phenotype relationship - a low protein expression of KCNJ5 relative to their peritumoural zona glomerulosa (ZG) and a zona fasciculata-like composition [5-6]. Conversely for the other genes, controversy arises on whether they have the opposite cell phenotype [4,7-8]...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27748439/targeting-of-cyp17a1-lyase-by-vt-464-inhibits-adrenal-and-intratumoral-androgen-biosynthesis-and-tumor-growth-of-castration-resistant-prostate-cancer
#14
Sankar N Maity, Mark A Titus, Revekka Gyftaki, Guanglin Wu, Jing-Fang Lu, S Ramachandran, Elsa M Li-Ning-Tapia, Christopher J Logothetis, John C Araujo, Eleni Efstathiou
Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) is a validated treatment target for the treatment of metastatic castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA) inhibits both 17α-hydroxylase (hydroxylase) and 17,20-lyase (lyase) reactions catalyzed by CYP17A1 and thus depletes androgen biosynthesis. However, coadministration of prednisone is required to suppress the mineralocorticoid excess and cortisol depletion that result from hydroxylase inhibition. VT-464, a nonsteroidal small molecule, selectively inhibits CYP17A1 lyase and therefore does not require prednisone supplementation...
October 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27748298/a-cross-sectional-study-to-assess-any-possible-linkage-of-c-t-polymorphism-in-cyp17a1-gene-with-insulin-resistance-in-non-obese-women-with-polycystic-ovarian-syndrome
#15
Ushasi Banerjee, Anindya Dasgupta, Aparna Khan, Mrinal Kanti Ghosh, Pranab Roy, Jayanta Kumar Rout, Priyankar Roy, Suparna Dhara
BACKGROUND & OBJECTIVES: Insulin resistance (IR) is a major confounding factor in polycystic ovarian syndrome (PCOS) irrespective of obesity. Its exact mechanism remains elusive till now. C/T polymorphism in the -34 promoter region of the CYP17 gene is inconsistently attributed to elucidate the mechanism of IR and its link to hyperandrogenemia in obese PCOS patients. In the present study we aimed to evaluate any association of this polymorphism with IR in non-obese women with PCOS. METHODS: Polymorphism study was performed by restriction fragment length polymorphism (RFLP) analysis of the Msp A1 digest of the PCR product of the target gene in 75 PCOS cases against 73 age and BMI matched control women...
June 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/27706926/discordant-genotyping-results-using-dna-isolated-from-anti-doping-control-urine-samples
#16
Eva Choong, Jenny J Schulze, Magnus Ericsson, Anders Rane, Lena Ekström
The UGT2B17 gene deletion polymorphism is known to correlate to urinary concentration of testosterone-glucuronide and hence this genotype exerts a large impact on the testosterone/epitestosterone (T/E) ratio, a biomarker for testosterone doping. The objective of this study was to assess if DNA isolated from athletes' urine samples (n = 713) obtained in routine doping controls could be targeted for genotyping analysis for future integration in the athlete's passport. A control population (n = 21) including both urine and blood DNA was used for genotyping concordance test...
October 5, 2016: Drug Testing and Analysis
https://www.readbyqxmd.com/read/27683267/effects-of-daily-exposure-to-saccharin-and-sucrose-on-testicular-biologic-functions-in-mice
#17
Ting Gong, Quan-Wei Wei, Da-Gan Mao, Kentaro Nagaoka, Gen Watanabe, Kazuyoshi Taya, Fang-Xiong Shi
Saccharin sodium consumption is considered safe and beneficial, owing to its very intense sweetness without any associated calories, but supporting scientific data remain sparse and controversial. Herein, we demonstrate that dose-response relationships existed with regard to administration of saccharin or sucrose to mice for 35 days, and this association involved testis-expressed sweet-tasting molecules (taste receptor type 1 subunit 3 [T1R3]; G protein alpha-gustducin [Galpha]). Mouse body weights and testis weights in middle- and low-dose saccharin-treated groups were increased with up-expressions of molecules involved in testicular sweet taste and steroidogenic (middle saccharin: steroidogenic acute regulatory protein [StAR]; P450 cholesterol side-chain cleavage enzyme [CYP11A1]; 17-alpha-hydroxylase/C17,20-lyase [CYP17A1]; low saccharin: StAR)...
December 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27683182/a-phase-ii-trial-of-abiraterone-combined-with-dutasteride-for-men-with-metastatic-castration-resistant-prostate-cancer
#18
Rana R McKay, Lillian Werner, Elahe A Mostaghel, Rosina Lis, Olga Voznesensky, Zhenwei Zhang, Brett T Marck, Alvin M Matsumoto, Liran Domachevsky, Katherine A Zukotynski, Manoj Bhasin, Glenn J Bubley, Bruce Montgomery, Philip W Kantoff, Steven P Balk, Mary-Ellen Taplin
PURPOSE: Despite the efficacy of abiraterone, a CYP17A1 inhibitor, in metastatic castration-resistant prostate cancer (CRPC), nearly all patients develop resistance. The purpose of this phase II study was to evaluate mechanisms of resistance to more complete androgen synthesis inhibition with abiraterone and dutasteride. EXPERIMENTAL DESIGN: Eligible patients with metastatic CRPC underwent a baseline metastasis biopsy. Patients received abiraterone and prednisone for two 4-week cycles...
September 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27643307/lbos-02-06-histopathological-specific-mutation-spectrum-of-aldosterone-producing-adenomas
#19
Elena Azizan, Norlela Sukor, Nor Azmi Kamaruddin, A Rahman A Jamal, Jiri Ceral, Miroslav Solar, Isa Mohamed Rose, Geok Chin Tan
OBJECTIVE: Aldosterone-producing adenoma (APA) is a common curable cause of hypertension. Somatic mutations in five genes (KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1) have been found to cause the excess aldosterone production of two thirds of APAs [1-4]. KCNJ5 mutant APAs, the most common and largest, had explicit genotype-phenotype relationship - a low protein expression of KCNJ5 relative to their peritumoural zona glomerulosa (ZG) and a zona fasciculata-like composition [5-6]. Conversely for the other genes, controversy arises on whether they have the opposite cell phenotype [4,7-8]...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27583544/influence-of-statins-on-survival-outcome-in-patients-with-metastatic-castration-resistant-prostate-cancer-treated-with-abiraterone-acetate
#20
Martin Boegemann, Katrin Schlack, Ann-Kathrin Fischer, Joachim Gerß, Julie Steinestel, Axel Semjonow, Andres Jan Schrader, Laura-Maria Krabbe
OBJECTIVE: Even though the exact mechanism is largely unknown until now, statins are supposed to improve survival outcomes in various malignancies. For prostate cancer however, statins are known to compete with dehydroepiandrosterone (DHEAS) for the transport into the cytosol both using the cell by the Solute Carrier Transporter and thus diminish the cellular uptake of DHEAS as a precursor of androgens. Abiraterone inhibits CYP17A1 and thus effectively decreases the production of all relevant androgens including DHEAS...
2016: PloS One
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