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https://www.readbyqxmd.com/read/28774688/prenatal-exposure-to-drinking-water-chlorination-by-products-cytochrome-p450-gene-polymorphisms-and-small-for-gestational-age-neonates
#1
Samuella G Bonou, Patrick Levallois, Yves Giguère, Manuel Rodriguez, Alexandre Bureau
Genetic susceptibility may modulate chlorination by-products (CBPs) effects on fetal growth, especially genes coding for the cytochrome P450 involved in the metabolism of CBPs and steroidogenesis. In a case-control study of 1432 mother-child pairs, we assessed the association between maternal and child single nucleotide polymorphisms (SNPs) within CYP1A2, CYP2A6, CYP2D6 and CYP17A1 genes and small-for-gestational-age neonates (SGA<10th percentile) as well as interaction between these SNPs and maternal exposure to trihalomethanes or haloacetic acids (HAAs) during the third trimester of pregnancy...
July 31, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28774496/adrenal-c11-oxy-c21-steroids-contribute-to-the-c11-oxy-c19-steroid-pool-via-the-backdoor-pathway-in-the-biosynthesis-and-metabolism-of-21-deoxycortisol-and-21-deoxycortisone
#2
Lise Barnard, Rachelle Gent, Desmaré van Rooyen, Amanda C Swart
21-Hydroxylase deficiency presents with increased levels of cytochrome P450 21-hydroxylase substrates, progesterone and 17α-hydroxyprogesterone, which have been implicated in the production of androgens via the backdoor pathway. This study shows the biosynthesis of C11-oxy C21 steroids, 21-deoxycortisol and 21-deoxycortisone, and their metabolism by steroidogenic enzymes in the backdoor pathway yielding novel steroid metabolites: 5α-pregnan-11β,17α-diol-3,20-dione; 5α-pregnan-17α-ol-3,11,20-trione; 5α-pregnan-3α,11β,17α-triol-20-one and 5α-pregnan-3α,17α-diol-11,20-dione...
July 31, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28765074/estrogenic-effects-associated-with-bisphenol-a-exposure-in-male-zebrafish-danio-rerio-is-associated-with-changes-of-endogenous-17%C3%AE-estradiol-and-gene-specific-dna-methylation-levels
#3
Fei Zhao, Penghao Wei, Jun Wang, Miao Yu, Xiaona Zhang, Hua Tian, Wei Wang, Shaoguo Ru
The binding affinity of bisphenol A (BPA) to estrogen receptors (ERs) is much lower than that of 17β-estradiol (E2), and whether there are other molecular mechanisms responsible for the estrogenic action of BPA in vivo currently remains unknown. The objective of this study was to explore the potential association between the estrogenic effect induced by bisphenol A in vivo and changes of endogenous E2 and gene specific DNA methylation levels. After a waterborne exposure of male zebrafish to 500, 1000, or 1500μg/L of BPA for 21d, vitellogenin (VTG) concentration in whole body homogenate, plasma E2 and testosterone levels, hepatic ERs mRNA expressions, gonadal cyp19a1a and cyp17a1 mRNA expressions, and methylation levels of hepatic esr1 and gonadal cyp19a1a's promoters were determined...
July 29, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28752602/alterations-in-the-steroid-biosynthetic-pathways-in-the-human-prefrontal-cortex-in-mood-disorders-a-postmortem-study
#4
Xin-Rui Qi, Sabina Luchetti, Ronald W H Verwer, Arja A Sluiter, Matthew R J Mason, Jiang-Ning Zhou, Dick F Swaab
Altered levels of steroids have been reported in the brain, cerebral spinal fluid and plasma of patients with mood disorders. Neuroimaging studies have reported both functional and structural alterations in mood disorders, for instance in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC). In order to determine whether the endogenous production of steroids is altered in the ACC and DLPFC of patients with major depressive disorder (MDD) or bipolar disorder (BPD), quantitative real-time PCR was performed to detect mRNA expression level of key enzymes in the steroid biosynthetic pathways...
July 27, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28740105/a-brief-exposure-to-cadmium-impairs-leydig-cell-regeneration-in-the-adult-rat-testis
#5
Xiaolong Wu, Xiaoling Guo, Huang Wang, Songyi Zhou, Lili Li, Xiaomin Chen, Guimin Wang, Jianpeng Liu, Hong-Shan Ge, Ren-Shan Ge
Cadmium is an endocrine disruptor, impairing male reproduction. The objective of this study is to investigate whether cadmium affects rat Leydig cell regeneration and to dissect the underlying mechanism. Adult male Sprague-Dawley rats received a single intraperitoneal injection (i.p.) of 0, 0.5 or 1.0 mg/kg of cadmium chloride, followed by ethane dimethane sulfonate (EDS) treatment to eliminate adult Leydig cells 20 days later. Compared to control (0 dose), cadmium treatment reduced serum testosterone levels by days 21, 35, and 56 after EDS treatment...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738285/molecular-assessment-characterization-and-differentiation-of-theca-stem-cells-imply-the-presence-of-mesenchymal-and-pluripotent-stem-cells-in-sheep-ovarian-theca-layer
#6
Samane Adib, Mojtaba Rezazadeh Valojerdi
The ability of ovarian theca stem cells to differentiate into oocyte and theca cells may lead to a major advancement in reproductive biology and infertility treatments. However, there is little information about function, growth and differentiation potential of these immature cells. In this study adult sheep theca stem cells (TSCs) characteristics, and differentiation potential into osteocyte-like cells (OSLCs), adipocyte-like cells (ALCs), theca progenitor-like cells (TPCs), and oocyte-like cells (OLCs) were investigated...
July 8, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28715929/molecular-interactions-of-bisphenols-and-analogs-with-glucocorticoid-biosynthetic-pathway-enzymes-an-in-silico-approach
#7
Garima Verma, Mohemmed Faraz Khan, Wasim Akhtar, Mohammad Mumtaz Alam, Mymoona Akhter, Mohammad Shaquiquzzaman
Glucocorticoids are known to have vital effects on metabolism, behavior and immunity. Any sort of impairment in their synthesis may lead to the generation of numerous ill health effects. Different environmental toxicants, including bisphenols and their analogs pose deleterious effect on the biosynthesis of glucocorticoids, thereby leading to endocrine disruption. In order to assess the effect of these environmental toxicants on gluocorticoid biosynthetic pathway, an in silico study was performed. This involved molecular docking studies of 18 ligands with the selected participating enzymes of the pathway...
July 17, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28710293/probing-gata-factor-function-in-mouse-leydig-cells-via-testicular-injection-of-adenoviral-vectors
#8
Gervette M Penny, Rebecca B Cochran, Marjut Pihlajoki, Antti Kyrönlahti, Anja Schrade, Merja Häkkinen, Jorma Toppari, Markku Heikinheimo, David B Wilson
Testicular Leydig cells produce androgens essential for proper male reproductive development and fertility. Here, we describe a new Leydig cell ablation model based on Cre/Lox recombination of mouse Gata4 and Gata6, two genes implicated in the transcriptional regulation of steroidogenesis. The testicular interstitium of adult Gata4(flox/flox);Gata6(flox/flox) mice was injected with adenoviral vectors encoding Cre + GFP (Ad-Cre-IRES-GFP) or GFP alone (Ad-GFP). The vectors efficiently and selectively transduced Leydig cells, as evidenced by GFP reporter expression...
July 14, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28707358/suppressed-oligodendrocyte-steroidogenesis-in-multiple-sclerosis-implications-for-regulation-of-neuroinflammation
#9
Roobina Boghozian, Brienne A McKenzie, Leina B Saito, Ninad Mehta, William G Branton, JianQiang Lu, Glen B Baker, Farshid Noorbakhsh, Christopher Power
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Neurosteroids are reported to exert anti-inflammatory effects in several neurological disorders. We investigated the expression and actions of the neurosteroid, dehydroepiandrosterone (DHEA), and its more stable 3β-sulphated ester, DHEA-S, in MS and associated experimental models. CNS tissues from patients with MS and animals with experimental autoimmune encephalomyelitis (EAE) displayed reduced DHEA concentrations, accompanied by diminished expression of the DHEA-synthesizing enzyme CYP17A1 in oligodendrocytes (ODCs), in association with increased expression of inflammatory genes including interferon (IFN)-γ and interleukin (IL)-1β...
July 14, 2017: Glia
https://www.readbyqxmd.com/read/28666831/steroidogenic-acute-regulatory-protein-star-gene-expression-construct-development-nanodelivery-and-effect-on-reproduction-in-air-breathing-catfish-clarias-batrachus
#10
Pravesh Kumar Rathor, Irfan Ahmad Bhat, Mohd Ashraf Rather, Pathakota Gireesh-Babu, Kundan Kumar, Suresh Babu Padinhate Purayil, Rupam Sharma
Steroidogenic acute regulatory protein (StAR) is responsible for the relocation of cholesterol across mitochondrial membrane in vertebrates and is, therefore, a key factor in regulating the rate and timing of steroidogenesis. In the present study, we developed chitosan nanoparticle (CNP) conjugated StAR gene construct (CNP-pcDNA4-StAR) in a eukaryotic expression vector, pcDNA4/HisMax A. CNPs of 135.4nm diameter, 26.7mV zeta potential and 0.381 polydispersity index were used for conjugation. The loading efficiency (LE) of pcDNA4-StAR construct with CNPs was found to be 86%...
June 27, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28665508/a-polymorphism-in-the-cyp17a1-gene-influences-the-therapeutic-response-to-steroidogenesis-inhibitors-in-cushing-s-syndrome
#11
Elena Valassi, Anna Aulinas, Camilla Am Glad, Gudmundur Johannsson, Oskar Ragnarsson, Susan M Webb
CONTEXT: Steroidogenesis inhibitors, such as ketoconazole (KTZ) and metyrapone (MTP) are used to lower hypercortisolism in patients with Cushing's syndrome (CS). Cortisol normalization is not reached in all patients taking these medications. OBJECTIVE: To test the hypothesis that variants in genes affecting steroidogenesis contribute to different responses to KTZ and/or MTP in patients with CS. PATIENTS AND METHODS: Fifty-four CS patients [46 women; mean (±SD) age, 39...
June 30, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28648378/steroidogenic-metabolism-of-galeterone-reveals-a-diversity-of-biochemical-activities
#12
Mohammad Alyamani, Zhenfei Li, Michael Berk, Jianneng Li, Jingjie Tang, Sunil Upadhyay, Richard J Auchus, Nima Sharifi
Galeterone is a steroidal CYP17A1 inhibitor, androgen receptor (AR) antagonist, and AR degrader, under evaluation in a phase III clinical trial for castration-resistant prostate cancer (CRPC). The A/B steroid ring (Δ(5),3β-hydroxyl) structure of galeterone is identical to that of cholesterol, which makes endogenous steroids with the same structure (e.g., dehydroepiandrosterone and pregnenolone) substrates for the enzyme 3β-hydroxysteroid dehydrogenase (3βHSD). We found that galeterone is metabolized by 3βHSD to Δ(4)-galeterone (D4G), which is further converted by steroid-5α-reductase (SRD5A) to 3-keto-5α-galeterone (5αG), 3α-OH-5α-galeterone, and 3β-OH-5α-galeterone; in vivo it is also converted to the three corresponding 5β-reduced metabolites...
July 20, 2017: Cell Chemical Biology
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
#13
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
#14
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 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
#15
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
#16
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
#17
I Savchuk, M L Morvan, J P Antignac, K Gemzell-Danielsson, B Le Bizec, O Söder, K 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...
August 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28592202/pharmacogenetics-and-aromatase-inhibitor-induced-side-effects-in-breast-cancer-patients
#18
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
#19
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
#20
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
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