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CYP17A1

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https://www.readbyqxmd.com/read/28924064/circulating-steroid-hormone-variations-throughout-different-stages-of-prostate-cancer
#1
Gido Snaterse, Jenny A Visser, Wiebke Arlt, Johannes Hofland
Steroid hormones play a central role in the maintenance and progression of prostate cancer. The androgen receptor is the primary driver of tumor cell proliferation and is activated by the androgens testosterone and 5α-dihydrotestosterone. Inhibition of this pathway through medical or surgical castration improves survival in the majority of advanced prostate cancer patients. However, conversion of adrenal androgen precursors and alternative steroidogenic pathways have been found to contribute to tumor progression and resistance to treatment...
September 18, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28893623/cyp17a1-inhibitor-abiraterone-an-anti-prostate-cancer-drug-also-inhibits-the-21-hydroxylase-activity-of-cyp21a2
#2
Jana Malikova, Simone Brixius-Anderko, Sameer S Udhane, Shaheena Parween, Bernhard Dick, Rita Bernhardt, Amit V Pandey
Abiraterone is an inhibitor of CYP17A1 which is used for the treatment of castration resistant prostate cancer. Abiraterone is known to inhibit several drug metabolizing cytochrome P450 enzymes including CYP1A2, CYP2D6, CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, but its effects on steroid metabolizing P450 enzymes are not clear. In preliminary results, we had observed inhibition of CYP21A2 by 1μM abiraterone. Here we are reporting the effect of abiraterone on activities of CYP21A2 in human adrenal cells as well as with purified recombinant CYP21A2...
September 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28890368/cyp17a1-independent-production-of-the-neurosteroid-derived-5%C3%AE-pregnan-3%C3%AE-6%C3%AE-diol-20-one-in-androgen-responsive-prostate-cancer-cell-lines-under-serum-starvation-and-inhibition-by-abiraterone
#3
Antonio G Gomes de Mello Martins, Giuseppe Allegretta, Gerhard Unteregger, Jörg Haupenthal, Jens Eberhard, Michael Hoffmann, Jill A van der Zee, Kerstin Junker, Michael Stöckle, Rolf Müller, Rolf W Hartmann, Carsten-H Ohlmann
CYP17A1-independent intratumoral steroid hormone synthesis is regarded as one possible explanation for resistance to treatment with the CYP17-inhibitor Abiraterone (Abi). The aim of our study was therefore to investigate the steroid metabolism of prostate cancer cells under serum starvation and the effects of Abi treatment. We assessed steroid metabolism in a panel of prostate cancer cells under serum starvation by radioactivity detector-coupled HPLC and HPLC-ESI-ToF-mass spectrometry after treatment with pregnenolone, progesterone and allopregnanolone...
September 7, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28878092/equine-fetal-adrenal-gonadal-and-placental-steroidogenesis
#4
Erin L Legacki, Barry A Ball, C Jo Corbin, Shavahn C Loux, Kirsten E Scoggin, Scott D Stanley, Alan J Conley
Equine fetuses have substantial circulating pregnenolone concentrations and thus have been postulated to provide significant substrate for placental 5α-reduced pregnane production, but the fetal site of pregnenolone synthesis remains unclear. The current studies investigated steroid concentrations in blood, adrenal glands, gonads and placenta from fetuses (4, 6, 9 and 10 months of gestational age (GA)), as well as tissue steroidogenic enzyme transcript levels. Pregnenolone and dehydroepiandrosterone (DHEA) were the most abundant steroids in fetal blood, pregnenolone was consistently higher but decreased progressively with GA...
October 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28870780/mutational-analysis-of-rare-subtypes-of-congenital-adrenal-hyperplasia-in-a-highly-inbred-population
#5
Meshael M Alswailem, Ohoud S Alzahrani, Doha S Alhomaidah, Rahma Alasmari, Ebtesam Qasem, Avaniyapuram Kannan Murugan, Afaf Alsagheir, Imad Brema, Bassam Ben Abbas, Mohammed Almehthel, Ali Almeqbali, Ali S Alzahrani
CONTEXT: Apart from 21 Hydroxylase deficiency, other subtypes of congenital adrenal hyperplasia (CAH) are rare. We studied the clinical features and molecular genetics of a relatively large series of patients with CYP17A1, HSD3β2 and StAR deficiencies. PATIENTS AND METHODS: We studied 21 patients including 7 patients with CYP17A1, 10 patients with HSD3β2 and 4 patients with StAR deficiencies. For mutation detection, we isolated DNA from peripheral leucocytes, amplified genes of interest using polymerase chain reaction and directly sequenced the amplicons using Dideoxy Chain Termination method...
September 6, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28852406/regulation-of-corticosteroidogenic-genes-by-micrornas
#6
Stacy Robertson, Louise A Diver, Samantha Alvarez-Madrazo, Craig Livie, Ayesha Ejaz, Robert Fraser, John M Connell, Scott M MacKenzie, Eleanor Davies
The loss of normal regulation of corticosteroid secretion is important in the development of cardiovascular disease. We previously showed that microRNAs regulate the terminal stages of corticosteroid biosynthesis. Here, we assess microRNA regulation across the whole corticosteroid pathway. Knockdown of microRNA using Dicer1 siRNA in H295R adrenocortical cells increased levels of CYP11A1, CYP21A1, and CYP17A1 mRNA and the secretion of cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone, and aldosterone...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28836396/morphological-and-molecular-aspects-of-in-vitro-culture-of-preantral-follicles-derived-from-vitrified-ovarian
#7
Mahboobeh Amoushahi, Mojdeh Salehnia, Seyed Javad Mowla, Nassim Ghorbanmehr
OBJECTIVE: This study aimed to evaluate the expression of the genes related to folliculogenesis after vitrification of mouse ovarian tissues using a two-step in vitro culture. MATERIALS AND METHODS: In this experimental study, vitrified and non-vitrified ovaries from 7- day old (neonate) female mice were cultured using alpha-Minimum Essential Medium (α-MEM) supplemented with 5% fetal bovine serum (FBS) for 7 days. Morphology, surface area of ovaries and percentage of normal follicles were evaluated and compared in both groups...
October 2017: Cell Journal
https://www.readbyqxmd.com/read/28827713/diethylstilbestrol-administration-inhibits-theca-cell-androgen-and-granulosa-cell-estrogen-production-in-immature-rat-ovary
#8
Yoshitaka Imamichi, Toshio Sekiguchi, Takeshi Kitano, Takashi Kajitani, Reiko Okada, Yoshihiko Inaoka, Kaoru Miyamoto, Junsuke Uwada, Satoru Takahashi, Takahiro Nemoto, Asuka Mano, Md Rafiqul Islam Khan, Md Tariqul Islam, Koh-Ichi Yuhki, Hitoshi Kashiwagi, Fumitaka Ushikubi, Nobuo Suzuki, Takanobu Taniguchi, Takashi Yazawa
Diethylstilbestrol (DES), a strong estrogenic compound, is well-known to affect the reproductive system. In this study, we investigated the effects of DES administration on gonadotropin levels and ovarian steroidogenesis in prepubertal rats. DES treatment acutely reduced serum LH levels, followed by a reduction in the expression of various steroidogenesis-related genes in theca cells. Serum FSH levels were almost unaffected by DES-treatment, even though Cyp19a1 expression was markedly reduced. Serum progesterone, testosterone and estradiol levels were also declined at this time...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28774688/prenatal-exposure-to-drinking-water-chlorination-by-products-cytochrome-p450-gene-polymorphisms-and-small-for-gestational-age-neonates
#9
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
#10
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
#11
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...
October 1, 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-post-mortem-study
#12
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
#13
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
#14
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
#15
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
#16
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...
October 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
#17
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
#18
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%...
November 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
#19
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
#20
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
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