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CYP17A1

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https://www.readbyqxmd.com/read/28634424/overexpression-and-knockdown-of-hypoxia-inducible-factor-1-disrupt-the-expression-of-steroidogenic-enzyme-genes-and-early-embryonic-development-in-zebrafish
#1
Tianfeng Tan, Richard Man Kit Yu, Rudolf Shiu Sun Wu, Richard Yuen Chong Kong
Hypoxia is an important environmental stressor leading to endocrine disruption and reproductive impairment in fish. Although the hypoxia-inducible factor 1 (HIF-1) is known to regulate the transcription of various genes mediating oxygen homeostasis, its role in modulating steroidogenesis-related gene expression remains poorly understood. In this study, the regulatory effect of HIF-1 on the expression of 9 steroidogenic enzyme genes was investigated in zebrafish embryos using a "gain-of-function and loss-of-function" approach...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28614857/combined-effect-of-the-pgr-331c%C3%A2-%C3%A2-t-cyp17a1-34a%C3%A2-%C3%A2-g-and-cyp19a1-1531g%C3%A2-%C3%A2-a-polymorphisms-on-the-risk-of-developing-endometriosis
#2
Jéssica Vilarinho Cardoso, Daniel Escorsim Machado, Renato Ferrari, Mayara Calixto da Silva, Plínio Tostes Berardo, Jamila Alessandra Perini
Purpose To evaluate the magnitude of the association of the polymorphisms of the genes PGR, CYP17A1 and CYP19A1 in the development of endometriosis. Methods This is a retrospective case-control study involving 161 women with endometriosis (cases) and 179 controls. The polymorphisms were genotyped by real-time polymerase chain reaction using the TaqMan system. The association of the polymorphisms with endometriosis was evaluated using the multivariate logistic regression. Results The endometriosis patients were significantly younger than the controls (36...
June 14, 2017: Revista Brasileira de Ginecologia e Obstetrícia
https://www.readbyqxmd.com/read/28611384/the-correlation-between-the-expression-of-genes-involved-in-drug-metabolism-and-the-blood-level-of-tacrolimus-in-liver-transplant-receipts
#3
Jianhai Wang, Keqiu Li, Xiaoning Zhang, Dahong Teng, Mingyan Ju, Yaqing Jing, Yuxia Zhao, Guang Li
Immunosuppressive medications, such as tacrolimus and mycophenolate mofetil, are commonly used for reducing the risk of organ rejection in receipts of allogeneic organ transplant. The optimal dosages of these drugs are required for preventing rejection and avoiding toxicity to receipts. This study aimed to identify the correlation between the expression profiling of genes involved in drug metabolism and the blood level of tacrolimus in liver transplant receipts. Sixty-four liver transplant receipts were enrolled in this retrospective study...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28609197/the-glu331del-mutation-in-the-cyp17a1-gene-causes-atypical-congenital-adrenal-hyperplasia-in-a-46-xx-female
#4
Giulia Lanzolla, Giuseppe Vancieri, Silvia Lanciotti, Federica Sangiuolo, Elisa Menegatti, Luca Federici, Costanzo Moretti, Francesco Brancati
17α-Hydroxylase deficiency is an uncommon type of congenital adrenal hyperplasia (CAH) caused by mutations in the CYP17A1 gene encoding both 17α-hydroxylase and 17,20-lyase, essential for sex steroids production. Main clinical features include lack of pubertal development, hypertension, and hypokalemia. We report the first case of a 46,XX female homozygote for the p.Glu331del mutation in the CYP17A1 gene showing an atypical clinical presentation. She was evaluated the first time for primary amenorrhea and delayed puberty in the presence of low levels of androgens, 17β-estradiol, serum cortisol, and high levels of progesterone and gonadotropins...
June 13, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28592511/androgenic-potential-of-human-fetal-adrenals-at-the-end-of-the-first-trimester
#5
Iuliia Savchuk, Marie-Line Morvan, Jean-Philippe Antignac, Kristina Gemzell-Danielsson, Bruno LeBizec, Olle Soder, Konstantin Svechnikov
The onset of steroidogenesis in human fetal adrenal glands (HFA) during the first trimester is poorly investigated. An unresolved question is the capacity of the HFA to produce potent androgen DHT via conventional and/or the backdoor pathway(s) at the end of first trimester, when androgen-responsive organs are developed. Our aim was to explore steroidogenesis and the expression of steroidogenic enzymes and transcription factors in HFA at gestational weeks (GW) 9-12 with focus on their androgenic potential. Steroids in the HFA were analyzed by gas chromatography/mass spectrometry...
June 7, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28592202/pharmacogenetics-and-aromatase-inhibitor-induced-side-effects-in-breast-cancer-patients
#6
Valentina Sini, Andrea Botticelli, Gianluigi Lunardi, Stefania Gori, Paolo Marchetti
This paper reviews genetic variations mainly related to the onset of adverse events during aromatase inhibitors in early breast cancer. Genetic variability could occur at different steps. The analysis included studies that involved breast cancer patients, treated with an aromatase inhibitor, genotyped for CYP19A1 and/or CYP17A1 and/or CYP27B1 and/or TCLA1, and/or RANK/RANKL/OPG and/or ESR1/ESR2, and assessed for toxicity profile. Twenty-two articles were included for the analysis. Three studies evaluated outcomes and adverse events; 19 studies assessed only side effects...
June 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28589964/hpa-axis-genes-and-their-interaction-with-childhood-maltreatment-are-related-to-cortisol-levels-and-stress-related-phenotypes
#7
Lotte Gerritsen, Yuri Milaneschi, Christiaan Vinkers, Bert van Hemert, Laura van Velzen, Lianne Schmaal, Brenda Wjh Penninx
Stress responses are controlled by the hypothalamus pituitary adrenal (HPA)-axis and maladaptive stress responses are associated with the onset and maintenance of stress-related disorders such as major depressive disorder (MDD). Genes that play a role in the HPA-axis regulation may likely contribute to the relation between relevant neurobiological substrates and stress-related disorders. Therefore, we performed gene-wide analyses for 30 a-priori literature-based genes involved in HPA-axis regulation in 2014 subjects (34% male; mean age: 42...
June 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28584016/aldosterone-producing-adenomas-histopathology-genotype-correlation-and-identification-of-a-novel-cacna1d-mutation
#8
Geok Chin Tan, Giulia Negro, Alexandra Pinggera, Nur Maya Sabrina Tizen Laim, Isa Mohamed Rose, Jiri Ceral, Ales Ryska, Long Kha Chin, Nor Azmi Kamaruddin, Norfilza Mohd Mokhtar, A Rahman A Jamal, Norlela Sukor, Miroslav Solar, Joerg Striessnig, Morris Jonathan Brown, Elena Aisha Azizan
Mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 are thought to cause the excessive autonomous aldosterone secretion of aldosterone-producing adenomas (APAs). The histopathology of KCNJ5 mutant APAs, the most common and largest, has been thoroughly investigated and shown to have a zona fasciculata-like composition. This study aims to characterize the histopathologic spectrum of the other genotypes and document the proliferation rate of the different sized APAs. Adrenals from 39 primary aldosteronism patients were immunohistochemically stained for CYP11B2 to confirm diagnosis of an APA...
July 2017: Hypertension
https://www.readbyqxmd.com/read/28579582/steroidogenic-enzyme-expression-in-estrogen-production-in-the-goat-gastrointestinal-gi-tract-and-the-effect-of-castration
#9
Hadi Mohibbi, Mohammad Ibrahim Qasimi, Kentaro Nagaoka, Gen Watanabe
Extragonadal tissues are known to produce estrogens. At these sites, the C19 precursor is important for aromatase expression for the production of estrogen. Aromatase expression is tissue-specific and is controlled by hormones. Recent studies have shown that rat gastric parietal cells expressed aromatase. Our first objective was to investigate steroidogenic enzyme expression in estrogen biosynthesis; the second objective was to investigate which site(s) of the GI tract expressed steroidogenic enzymes; and the third objective was to assess the effects of castration on steroidogenic enzyme expression...
June 2, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28575284/role-of-heat-shock-factor-1-in-conserving-cholesterol-transportation-in-leydig-cell-steroidogenesis-via-steroidogenic-acute-regulatory-protein
#10
Shintaro Oka, Koji Shiraishi, Mitsuaki Fujimoto, Arpit Katiyar, Ryosuke Takii, Akira Nakai, Hideyasu Matsuyama
Testicular testosterone synthesis begins with cholesterol transport into mitochondria via steroidogenic acute regulatory protein (StAR) in Leydig cells. Acute heat stress is known to obstruct testicular steroidogenesis by transcriptional repression of StAR. In contrast, chronic heat stress such as cryptorchidism or varicocele generally does not affect testicular steroidogenesis, suggesting that Leydig cells adapt to heat stress and retain their steroid synthesis ability. However, the mechanisms of the stress response in steroid-producing cells are unclear...
May 29, 2017: Endocrinology
https://www.readbyqxmd.com/read/28572510/the-bmp4-smad-signaling-pathway-regulates-hyperandrogenism-development-in-a-female-mouse-model
#11
Yang Liu, Shao-Yue Du, Meng Ding, Xin Dou, Fei-Fei Zhang, Zhi-Yong Wu, Shu-Wen Qian, Wei Zhang, Qi-Qun Tang, Cong-Jian Xu
Polycystic ovary syndrome (PCOS) is a common endocrine disorder and a major cause of anovulatory sterility in women at reproductive age. Most patients with PCOS have hyperandrogenism, caused by excess androgen synthesis. Bone morphogenetic protein 4 (BMP4) is an essential regulator of embryonic development and organ formation, and recent studies have also shown that BMP4 may be involved in female steroidogenesis process. However, effect of BMP4 on hyperandrogenism remains unknown. Here, using a female mouse model of hyperandrogenism, we found that ovarian BMP4 levels were significantly decreased in hyperandrogenism...
June 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28537227/association-of-cyp17a1-genetic-polymorphisms-and-susceptibility-to-essential-hypertension-in-the-southwest-han-chinese-population
#12
Qian Li, Tangxin Gao, Yuncang Yuan, Yanrui Wu, Qionglin Huang, Fei Xie, Pengzhan Ran, Lijuan Sun, Chunjie Xiao
BACKGROUND The CYP17A1 gene encodes for cytochrome P450 enzyme CYP17A1, which is involved with the steroidogenic pathway including mineralocorticoids. The CYP17A1 polymorphisms might affect enzyme activity, then leading to a state of mineralocorticoid 11-deoxycorticosterone excess characterized by hypertension, suppressed plasma renin activity, and low aldosterone concentrations. The aim of this study was to investigate the contribution of CYP17A1 polymorphisms in inducing the susceptibility to essential hypertension among the Southwest Han Chinese population...
May 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28530704/upregulation-of-cyp17a1-by-sp1-mediated-dna-demethylation-confers-temozolomide-resistance-through-dhea-mediated-protection-in-glioma
#13
J-Y Chuang, W-L Lo, C-Y Ko, S-Y Chou, R-M Chen, K-Y Chang, J-J Hung, W-C Su, W-C Chang, T-I Hsu
Steroidogenesis-mediated production of neurosteroids is important for brain homeostasis. Cytochrome P450 17A1 (CYP17A1), which converts pregnenolone to dehydroepiandrosterone (DHEA) in endocrine organs and the brain, is required for prostate cancer progression and acquired chemotherapeutic resistance. However, whether CYP17A1-mediated DHEA synthesis is involved in brain tumor malignancy, especially in glioma, the most prevalent brain tumor, is unknown. To investigate the role of CYP17A1 in glioma, we determined that CYP17A1 expression is significantly increased in gliomas, which secrete more DHEA than normal astrocytes...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28501544/the-dna-methylation-status-alteration-of-two-steroidogenic-genes-in-gonads-of-rare-minnow-after-bisphenol-a-exposure
#14
Ting Zhang, Yan Liu, Hong Chen, Jiancao Gao, Yingying Zhang, Cong Yuan, Zaizhao Wang
Both cytochrome P450c17 (CYP17A1) and P-450 side chain cleavage (CYP11A1) play important roles in steroid biosynthesis. According to our previous studies, bisphenol A (BPA) could regulate the mRNA expression of cyp17a1 and cyp11a1 in rare minnow Gobiocypris rarus. However, the potential mechanism of the regulation is barely understood. In the present study, aiming to explore how BPA affects the mRNA expression of cyp17a1 and cyp11a1 in testes and ovaries of G. rarus, we firstly cloned 340-bp fragment of 5' flanking region of cyp11a1 and then detected the methylation level of CpG loci involved in 5' flanking of cyp11a1 and cyp17a1 and their mRNA expression levels...
May 10, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28494548/-the-role-of-cytochrome-p450-in-nonalcoholic-fatty-liver-induced-by-high-fat-diet-a-gene-expression-profile-analysis
#15
Y Liu, F Cheng, Y X Luo, P Hu, H Ren, M L Peng
Objective: To clarify the role of cytochrome P450 in nonalcoholic fatty liver disease (NAFLD) by RNA-Seq and bioinformatics analysis. Methods: A total of 20 male C57BL/6 mice were used. Ten mice were fed with high-fat diet (D12492, 60% kcal fat) for 16 weeks to establish a mouse model of NAFLD, and the other 10 mice were fed with low-fat diet (D12450B, 10% kcal fat) as control group. At the end of the experiment, the body weight, liver weight, and hepatic triglyceride (TG) content were measured. Meanwhile, HE staining and RNA-Seq analysis were performed for the liver tissues...
April 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28487303/female-phenotype-with-male-karyotype-a-clinical-enigma
#16
Suja Sukumar, Pavan Uppula, Santosh Kumar, Anil Bhansali
Development of gonadal and phenotypic sex during embryogenesis invariably corresponds to the genotypic sex. However, some disorders of sex development are associated with discordance between the chromosomal, gonadal or phenotypic sex which include complete androgen insensitivity syndrome, 46XY complete gonadal dysgenesis (Swyer syndrome) and, rarely, congenital adrenal hyperplasia due to CYP 17A1 (17α-hydroxylase) deficiency. The enzyme CYP17A1 includes 17α-hydroxylase and 17,20-lyase which are required for the synthesis of cortisol and sex steroids, respectively...
May 9, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28445152/multiplexed-gene-expression-profiling-identifies-the-fgfr4-pathway-as-a-novel-biomarker-in-intrahepatic-cholangiocarcinoma
#17
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...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28432272/establishment-of-an-in-vitro-culture-model-of-theca-cells-from-hierarchical-follicles-in-ducks
#18
Xiang Gan, Da Chen, Yan Deng, Jusong 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 the present 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 (IF) showed that all inoculated cells could be stained by the CYP17A1/19A1 antibody but not by the FSHR antibody, which could stain granulosa cells...
June 30, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28432091/suppressive-effects-of-tnf%C3%AE-il6-and-macrophages-on-thecal-androgen-production
#19
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
#20
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...
May 4, 2017: Journal of Physical Chemistry Letters
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