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CYP17A1

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https://www.readbyqxmd.com/read/28445152/multiplexed-gene-expression-profiling-identifies-the-fgfr4-pathway-as-a-novel-biomarker-in-intrahepatic-cholangiocarcinoma
#1
Changhoon Yoo, Jihoon Kang, Deokhoon Kim, Kyu-Pyo Kim, Baek-Yeol Ryoo, Seung-Mo Hong, Jung Jin Hwang, Seong-Yun Jeong, Shin Hwang, Ki-Hun Kim, Young-Joo Lee, Klaus P Hoeflich, Oleg Schmidt-Kittler, Stephen Miller, Eun Kyung Choi
BACKGROUND: The fibroblast growth factor receptor 4 (FGFR4) pathway is an essential regulatory component of bile acid synthesis, and its relationship with hepatocellular carcinoma (HCC) has been reported. We investigated the gene expression and clinical significance of FGFR4 and related pathways in intrahepatic cholangiocarcinoma (iCCA). RESULTS: The median age was 56 years (range 30-78) and 34 patients (74%) were male. Six patients (13%) had hepatitis B virus infection, with or without liver cirrhosis...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28432272/establishment-of-an-in-vitro-culture-model-of-theca-cells-from-hierarchical-follicles-in-ducks
#2
Xiang Gan, da Chen, Yan Deng, Junsong Yuan, Bo Kang, Jiamin Qiu, Wenqiang Sun, Chunchun Han, Jiwei Hu, Liang Li, Jiwen Wang
Theca cells, including theca interna cells and theca externa cells, are vital components of ovarian follicles. The aim of this study is to identify a reliable method for the in vitro culture of theca cells from duck ovarian hierarchical (F4-F2) follicles. We improved the method for cell separation by using trypsin to further remove granular cells, and we increased the concentration of fetal bovine serum used in in vitro culture to improve cytoactivity. Cell antibody immunofluorescence showed that all inoculated cells could be stained by the CYP17A1/19A1 antibody but not by the FSHR antibody, which could stain granulosa cells...
April 21, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28432091/suppressive-effects-of-tnf%C3%AE-il6-and-macrophages-on-thecal-androgen-production
#3
Moafaq S Samir, Claire Glister, Dareen Mattar, Mhairi Laird, Philip G Knight
Pro-inflammatory cytokines secreted by macrophages and other cell-types are implicated as intra-ovarian factors affecting different aspects of ovarian function including follicle and corpus luteum 'turnover', steroidogenesis and angiogenesis. Here, we compared granulosal (GC) and thecal (TC) expression of TNF, IL6 and their receptors (TNFR1, TNFRSF1B, IL6R) during bovine antral follicle development; all five mRNA transcripts were detected in both GC and TC and statistically significant cell-type and follicle stage-related differences were evident...
April 21, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28423275/single-or-multiple-access-channels-to-the-cyp450s-active-site-an-answer-from-free-energy-simulations-of-the-human-aromatase-enzyme
#4
Alessandra Magistrato, Jacopo Sgrignani, Rolf Krause, Andrea Cavalli
Cytochromes P450 (CYP450s), in particular, CYP19A1 and CYP17A1, are key clinical targets of breast and prostate anticancer therapies, critical players in drug metabolism, and their overexpression in tumors is associated with drug resistance. In these enzymes, ligand (substrates, drugs) metabolism occurs in deeply buried active sites accessible only via several grueling channels, whose exact biological role remains unclear. Gaining direct insights on the mechanism by which ligands travel in and out is becoming increasingly important given that channels are involved in the modulation of binding/dissociation kinetics and the specificity of ligands toward a CYP450...
April 24, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28387522/mechanism-of-cytochrome-p450-17a1-catalyzed-hydroxylase-and-lyase-reactions
#5
Silvia Bonomo, Flemming Steen Jørgensen, Lars Olsen
Cytochrome P450 17A1 (CYP17A1) catalyzes C17 hydroxylation of pregnenolone and progesterone and the subsequent C17-C20 bond cleavage (lyase reaction) to form androgen precursors. Compound I (Cpd I) and peroxo anion (POA) are the heme-reactive species underlying the two reactions. We have characterized the reaction path for both the hydroxylase and lyase reactions using density functional theory (DFT) calculations and the enzyme-substrate interactions by molecular dynamics (MD) simulations. Activation barriers for positions subject to hydroxylase reaction have values close to each other and span from 54 to 60 kJ·mol(-1) with a small preference for 17α hydroxylation, in agreement with experimental observations...
April 19, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28376482/discordant-genotypic-sex-and-phenotype-variations-in-two-spanish-siblings-with-17%C3%AE-hydroxylase-17-20-lyase-deficiency-carrying-the-most-prevalent-mutated-cyp17a1-alleles-of-brazilian-patients
#6
Mónica Fernández-Cancio, Emilio García-García, Carmen González-Cejudo, María-Angeles Martínez-Maestre, Miguel-Angel Mangas-Cruz, Gil Guerra-Junior, Maricilda Pandi de Mello, Ivo J P Arnhold, Mirian Y Nishi, Berenice Bilharinho Mendonça, Elena García-Arumí, Laura Audí, Eduardo Tizzano, Antonio Carrascosa
17α-hydroxylase/17,20-lyase deficiency is a rare form of congenital adrenal hyperplasia caused by mutations in CYP17A1. Two phenotypic female sisters, aged 17 and 15 years and with 46,XY and 46,XX karyotypes, respectively, presented with primary amenorrhea and absent secondary sexual characteristics. The elder sib also presented with high blood pressure. Both patients had elevated levels of ACTH, gonadotropins, progesterone, corticosterone, and deoxycorticosterone, and reduced levels of estradiol, testosterone, androstenedione, 17-OH-P, DHEA-S, cortisol, aldosterone, and renin activity...
April 4, 2017: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
https://www.readbyqxmd.com/read/28373265/structural-and-functional-evaluation-of-clinically-relevant-inhibitors-of-steroidogenic-cytochrome-p450-17a1-cyp17a1
#7
Elyse M Petrunak, Steven A Rogers, Jeffrey Aube, Emily E Scott
Human steroidogenic cytochrome P450 17A1 (CYP17A1) is a bifunctional enzyme that performs both hydroxylation and lyase reactions, with the latter required to generate androgens that fuel prostate cancer proliferation. The steroid abiraterone, the active form of the only FDA- approved CYP17A1 inhibitor, binds the catalytic heme iron, nonselectively impeding both reactions and ultimately causing undesirable corticosteroid imbalance. Some non-steroidal inhibitors reportedly inhibit the lyase reaction more than the preceding hydroxylase reaction, which would be clinically advantageous, but the mechanism is not understood...
April 3, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28348047/genome-wide-association-study-meta-analysis-of-long-term-average-blood-pressure-in-east-asians
#8
Changwei Li, Yun Kyoung Kim, Rajkumar Dorajoo, Huaixing Li, I-Te Lee, Ching-Yu Cheng, Meian He, Wayne H-H Sheu, Xiuqing Guo, Santhi K Ganesh, Jiang He, Juyoung Lee, Jianjun Liu, Yao Hu, Dabeeru C Rao, Fuu-Jen Tsai, Jia Yu Koh, Hua Hu, Kae-Woei Liang, Walter Palmas, James E Hixson, Sohee Han, Yik-Ying Teo, Yiqin Wang, Jing Chen, Chieh Hsiang Lu, Yingfeng Zheng, Lixuan Gui, Wen-Jane Lee, Jie Yao, Dongfeng Gu, Bok-Ghee Han, Xueling Sim, Liang Sun, Jinying Zhao, Chien-Hsiun Chen, Neelam Kumari, Yunfeng He, Kent D Taylor, Leslie J Raffel, Sanghoon Moon, Jerome I Rotter, Yii-der Ida Chen, Tangchun Wu, Tien Yin Wong, Jer-Yuarn Wu, Xu Lin, E-Shyong Tai, Bong-Jo Kim, Tanika N Kelly
BACKGROUND: Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP. METHODS AND RESULTS: We conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a P<5.0×10(-8) and 2.5×10(-)(6), respectively, in joint analyses of stage-1 and stage-2 data...
April 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28323049/sutherlandia-frutescens-modulates-adrenal-hormone-biosynthesis-displays-anti-mineralocorticoid-and-serga-properties-acting-as-a-dissociated-glucocorticoid
#9
C A Sergeant, D Africander, P Swart, A C Swart
ETHNOPHARMACOLOGICAL RELEVANCE: Sutherlandia frutescens is a traditional African medicinal plant used in the treatment of stress and anxiety, while also exhibiting anti-inflammatory properties. AIM OF STUDY: The study aimed at linking anti-stress and anti-inflammatory properties of S. frutescens to its influence on glucocorticoid biosynthesis and the inflammatory response via steroid receptor interaction. MATERIALS AND METHODS: The influence of S...
March 18, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28304025/illuminating-cytochrome-p450-binding-ru-ii-caged-inhibitors-of-cyp17a1
#10
Ao Li, Rahul Yadav, Jessica K White, Mackenzie K Herroon, Brian P Callahan, Izabela Podgorski, Claudia Turro, Emily E Scott, Jeremy J Kodanko
New Ru(ii)-caged abiraterone complexes were synthesized that exhibit strong absorption in the visible region and release the steroidal CYP17A1 inhibitor abiraterone upon exposure to low energy visible light in buffer and prostate cancer cells. Photoinduced release results in abiraterone binding to its CYP17A1 target in an inhibitory mode.
March 28, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28281692/ibuprofen-results-in-alterations-of-human-fetal-testis-development
#11
Millissia Ben Maamar, Laurianne Lesné, Kristin Hennig, Christèle Desdoits-Lethimonier, Karen R Kilcoyne, Isabelle Coiffec, Antoine D Rolland, Cécile Chevrier, David M Kristensen, Vincent Lavoué, Jean-Philippe Antignac, Bruno Le Bizec, Nathalie Dejucq-Rainsford, Rod T Mitchell, Séverine Mazaud-Guittot, Bernard Jégou
Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7-17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8-9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28272372/acth-and-polymorphisms-at-steroidogenic-loci-as-determinants-of-aldosterone-secretion-and-blood-pressure
#12
REVIEW
Scott M MacKenzie, E Marie Freel, John M Connell, Robert Fraser, Eleanor Davies
The majority of genes contributing to the heritable component of blood pressure remain unidentified, but there is substantial evidence to suggest that common polymorphisms at loci involved in the biosynthesis of the corticosteroids aldosterone and cortisol are important. This view is supported by data from genome-wide association studies that consistently link the CYP17A1 locus to blood pressure. In this review article, we describe common polymorphisms at three steroidogenic loci (CYP11B2, CYP11B1 and CYP17A1) that alter gene transcription efficiency and levels of key steroids, including aldosterone...
March 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28261922/a-case-of-primary-aldosteronism-caused-by-unilateral-multiple-adrenocortical-micronodules-presenting-as-muscle-cramps-at-rest-the-importance-of-functional-histopathology-for-identifying-a-culprit-lesion
#13
Atsushi Ito, Yuto Yamazaki, Hironobu Sasano, Daisuke Matsubara, Noriyoshi Fukushima, Mio Tamba, Kenichi Tabata, Kentaro Ashizawa, Akihito Takei, Masaru Koizumi, Yasunaru Sakuma, Naohiro Sata, Hisashi Oshiro
Unilateral multiple adrenocortical micronodules (UMNs) constitute a rare subset of primary aldosteronism (PA) characterized by the hypersecretion of aldosterone derived from multiple small nodules in the zona glomerulosa of the unilateral adrenal grand. This case study describes a 49-year-old man with PA and UMNs who presented with muscle cramps at rest due to hypokalemia. The patient had a 6-year history of hypertension treated with antihypertensive drugs. Imaging studies revealed bilateral adrenal nodules as large as 5 mm...
April 2017: Pathology International
https://www.readbyqxmd.com/read/28245012/structure-based-optimisation-of-non-steroidal-cytochrome-p450-17a1-inhibitors
#14
Morten Larsen, Cecilie H Hansen, Tobias B Rasmussen, Julie Islin, Bjarne Styrishave, Lars Olsen, Flemming Steen Jørgensen
Five new non-steroidal inhibitors for cytochrome P450 17A1 (CYP17A1) were identified by structure-based optimisation from a recently identified selective CYP17A1 inhibitor. The compounds are nanomolar inhibitors of steroidogenesis measured in recombinant CYP17A1 and in H295R cells.
February 28, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28243257/identification-of-stem-leydig-cells-derived-from-pig-testicular-interstitium
#15
Shuai Yu, Pengfei Zhang, Wuzi Dong, Wenxian Zeng, Chuanying Pan
Stem Leydig cells (SLCs), located in the testicular interstitial compartment in the mammalian testes, are capable of differentiating to testosterone-synthesizing Leydig cells (LCs), thus providing a new strategy for treating testosterone deficiency. However, no previous reports have identified and cultured SLCs derived from the pig. The aim of the current study was to isolate, identify, and culture SLCs from pigs. Haematoxylin and eosin staining and immunochemical analysis showed that SLCs were present and that PDGFRα was mainly expressed in the pig testicular interstitium, indicating that PDGFRα was a marker for SLCs in the neonatal pig...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28238672/thermodynamics-of-interactions-between-mammalian-cytochromes-p450-and-b5
#16
Evgeny Yablokov, Anna Florinskaya, Alexei Medvedev, Gennady Sergeev, Natallia Strushkevich, Alexander Luschik, Tatsiana Shkel, Irina Haidukevich, Andrei Gilep, Sergey Usanov, Alexis Ivanov
Cytochromes P450 (CYPs) play an important role in the metabolism of xenobiotics and various endogenous substrates. Being a crucial component of the microsomal monooxygenase system, CYPs are involved in numerous protein-protein interactions. However, mechanisms underlying molecular interactions between components of the monooxygenase system still need better characterization. In this study thermodynamic parameters of paired interactions between mammalian CYPs and cytochromes b5 (CYB5) have been evaluated using a Surface Plasmon Resonance (SPR) based biosensor Biacore 3000...
April 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28225307/17a-hydroxylase-17-20-lyase-deficiency-clinical-and-molecular-characterization-of-eight-chinese-patients
#17
Chaoming Wu, Shanshan Fan, Yanying Qian, Yingying Zhou, Jian Jin, Zhijuan Dai, Ling Jiang
BACKGROUND: 17α-hydroxylase/17, 20-lyase deficiency (17OHD) is caused by mutations in CYP17A1 gene. OBJECTIVE: To better understand 17OHD, a rare disease, we described the clinical features and analyzed the CYP17A1 gene in eight affected Chinese patients. METHODS: Patients with complete (7/8) or partial (1/8) 17OHD were derived from six families. The diagnosis was established according to their clinical, biochemical, hormonal and radiological characteristics...
February 22, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28213303/diethylstilbestrol-flutamide-and-their-combination-impaired-the-spermatogenesis-of-male-adult-zebrafish-through-disrupting-hpg-axis-meiosis-and-apoptosis
#18
Pan Yin, Ying-Wen Li, Qi-Liang Chen, Zhi-Hao Liu
Both diethylstilbestrol (DES, an environmental estrogen) and flutamide (FLU, an anti-androgen) are found to impair spermatogenesis by disrupting hypothalamic-pituitary-gonadal (HPG) axis and altering androgen levels through different mechanisms/modes of action in fish with poorly understood underlying mechanisms. Furthermore, it is not known whether and how a combined exposure of DES and FLU has a stronger effect than the compounds alone. In this study, male zebrafish adults were exposed to DES, FLU and their combination (DES+FLU) for 30days, and their effects on histological structure and sperm count in testis, androgen level in plasma, as well as the mRNA levels of genes involved in HPG axis, meiotic regulation and apoptosis were analyzed...
April 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28166986/testicular-gene-expression-of-steroidogenesis-related-factors-in-prepubertal-postpubertal-and-aging-dogs
#19
E Ogawa, N Kawate, T Inaba, H Tamada
Developmental and aging changes in testicular factors related to steroidogenesis are unknown in dogs. Using reverse transcription quantitative real-time PCR, this study examined testicular mRNA levels of CYP11A1 (P450 cholesterol side-chain cleavage enzyme, P450scc), CYP17A1 (P450 17α-hydroxylase/C17-20 lyase, P450c17), HSD3B2 (3β-hydroxysteroid dehydrogenase, 3β-HSD), CYP19A (P450 aromatase, P450arom), STAR (steroidogenic acute regulatory protein, StAR), cyclooxygenase (COX) -1 and COX-2 in prepubertal (4-6 months of age), postpubertal (1 year of age), and aging (2-18 years of age) dogs...
March 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28166973/short-term-hypertonic-exposure-enhances-in%C3%A2-vitro-follicle-growth-and-meiotic-competence-of-enclosed-oocytes-while-modestly-affecting-mrna-expression-of-aquaporin-and-steroidogenic-genes-in-the-domestic-cat-model
#20
N Songsasen, C Thongkittidilok, K Yamamizu, D E Wildt, P Comizzoli
Using the domestic cat as a non-rodent, larger animal model, the objective was to determine the impact of a brief incubation in a hypertonic microenvironment on (1) ovarian follicle and oocyte growth in vitro, (2) developmental capacity of the resident oocyte, and (3) expression of aquaporin (AQP) genes in parallel with genes involved in regulation of folliculogenesis. In Study 1: Secondary or early antral follicles encapsulated in 0.5% alginate were allocated to one of three treatment groups: 1) culture in standard medium at 290 mOsm for 15 d (Control); 2) incubation in 350 mOsm medium for 1 h followed by culture in standard medium for 15 d (Hypertonic-1h); or 3) incubation in 350 mOsm medium for 24 h followed by incubation in standard medium for additional 14 d (Hypertonic-24h)...
March 1, 2017: Theriogenology
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