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CYP17A1

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https://www.readbyqxmd.com/read/28323049/sutherlandia-frutescens-modulates-adrenal-hormone-biosynthesis-displays-anti-mineralocorticoid-and-serga-properties-acting-as-a-dissociated-glucocorticoid
#1
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
#2
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 17, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28281692/ibuprofen-results-in-alterations-of-human-fetal-testis-development
#3
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
#4
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
#5
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...
March 5, 2017: Pathology International
https://www.readbyqxmd.com/read/28245012/structure-based-optimisation-of-non-steroidal-cytochrome-p450-17a1-inhibitors
#6
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
#7
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
#8
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...
February 24, 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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28166959/the-effect-of-orexin-a-on-cyp17a1-and-cyp19a3-expression-and-on-oestradiol-oestrone-and-testosterone-secretion-in-the-porcine-uterus-during-early-pregnancy-and-the-oestrous-cycle
#13
Marta Kiezun, Nina Smolinska, Kamil Dobrzyn, Karol Szeszko, Edyta Rytelewska, Tadeusz Kaminski
Orexin A (OXA) is a hypothalamic neuropeptide known for its role in the regulation of food intake and arousal. It is also considered as a link between energy homeostasis and reproduction. Nevertheless, very little is known on the role of this peptide in the uterus. The objective of this study was to investigate OXA effect on oestradiol (E2), oestrone (E1), and testosterone (T) secretion by porcine endometrial and myometrial explants and gene expression of key steroidogenic enzymes involved in steroid production, namely cytochrome P450c17 (CYP17A1) and cytochrome P450 aromatase (CYP19A3), on days 10-11, 12 to 13, 15 to 16 and 27 to 28 of pregnancy and on days 10-11 of the cycle...
March 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28157646/polymorphism-in-xenobiotic-and-estrogen-metabolizing-genes-exposure-to-perfluorinated-compounds-and-subsequent-breast-cancer-risk-a-nested-case-control-study-in-the-danish-national-birth-cohort
#14
Mandana Ghisari, Manhai Long, Durita Mohr Røge, Jørn Olsen, Eva C Bonefeld-Jørgensen
In the present case-cohort study based on prospective data from Danish women, we aimed to estimate the main effect of polymorphisms in genes known to be involved in the steroid hormone metabolic pathway and xenobiotic metabolism on the risk of developing breast cancer. We also studied a possible effect measure modification between genotypes and levels of serum perfluoroalkylated substances (PFASs) on the risk to breast cancer. We have previously reported a weak association between serum PFASs levels and the risk of breast cancer for this study population of Danish pregnant nulliparous women as well as in a smaller case-control study of Greenlandic women...
April 2017: Environmental Research
https://www.readbyqxmd.com/read/28130116/diagnostic-yield-of-targeted-gene-panel-sequencing-to-identify-the-genetic-etiology-of-disorders-of-sex-development
#15
Ja Hye Kim, Eungu Kang, Sun Hee Heo, Gu-Hwan Kim, Ja-Hyun Jang, Eun-Hae Cho, Beom Hee Lee, Han-Wook Yoo, Jin-Ho Choi
Disorders of sex development (DSD) vary phenotypically and are caused by a number of genetic etiologies. This study investigated the genetic etiology of DSD patients using targeted exome sequencing of 67 known DSD-associated genes in humans. This study included 37 patients with 46, XY DSD and seven patients with 46, XX DSD. We identified known pathogenic mutations or deletion in nine (20.5%) patients in the AR, CYP17A1, SRD5A1, and DMRT1/2 genes. Novel variants were identified in nine patients (20.5%) in the AR, ATRX, CYP17A1, CHD7, MAP3K1, NR5A1, and WWOX genes...
January 24, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28128864/aliphatic-c-c-bond-cleavage-in-%C3%AE-hydroxy-ketones-by-a-dioxygen-derived-nucleophilic-iron-oxygen-oxidant
#16
Shrabanti Bhattacharya, Rubina Rahaman, Sayanti Chatterjee, Tapan K Paine
A nucleophilic iron-oxygen oxidant, formed in situ in the reaction between an iron(II)-benzilate complex and O2 , oxidatively cleaves the aliphatic C-C bonds of α-hydroxy ketones. In the cleavage reaction, α-hydroxy ketones without any α-C-H bond afford a 1:1 mixture of carboxylic acid and ketone. Isotope labeling studies established that one of the oxygen atoms from dioxygen is incorporated into the carboxylic acid product. Furthermore, the iron(II) complex cleaves an aliphatic C-C bond of 17-α-hydroxyprogesterone affording androstenedione and acetic acid...
January 27, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28115581/differential-expression-of-cart-in-ewes-with-differing-ovulation-rates
#17
Jennifer L Juengel, Michelle C French, Laurel D Quirke, Alexia Kauff, George W Smith, Peter D Johnstone
We hypothesised that cocaine- and amphetamine-regulated transcript (CARTPT) would be differentially expressed in ewes with differing ovulation rates. Expression of mRNA for CARTPT, as well as LHCGR, FSHR, CYP19A1 and CYP17A1 was determined in antral follicles >1 mm in diameter collected during the follicular phase in ewes heterozygous for the Booroola and Inverdale genes (I+B+; average ovulation rate 4) and ++ contemporaries (++; average ovulation rate 1.8). In ++ ewes (n=6), CARTPT was expressed in small follicles (1-<3 mm diameter), where 18...
January 23, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28109954/a-role-of-kit-receptor-signaling-for-proliferation-and-differentiation-of-rat-stem-leydig-cells-in%C3%A2-vitro
#18
Shiwen Liu, Xiaomin Chen, Yiyan Wang, Linxi Li, Guimin Wang, Xiaoheng Li, Haolin Chen, Jingjing Guo, Han Lin, Qing-Quan Lian, Ren-Shan Ge
In the testis, KIT ligand (KITL, also called stem cell factor) is expressed by Sertoli cells and its receptor (c-kit, KIT) is expressed by spermatogonia and Leydig cells. Although KITL-KIT signaling is critical for the spermatogenesis, its roles in Leydig cell development during puberty are not clear. In the present study, we investigated effects of KITL on stem Leydig cell proliferation and differentiation. Using an in vitro culture system of seminiferous tubules from Leydig cell-depleted testis, we found that KITL increased the proliferation activity of putative stem Leydig cells at higher concentration (10 and 100 ng/ml)...
January 18, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28105631/association-of-genetic-variation-with-blood-pressure-traits-among-east-africans
#19
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
#20
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
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