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Journal of Steroid Biochemistry and Molecular Biology

Ronda Greaves, Stefan A Wudy, Emilio Badoer, Margaret Zacharin, Jonathan J Hirst, Tracey Quinn, David W Walker
DHEA and DHEAS are neuroactive neurosteroids that interact with several major receptor system in the brain, including sigma (σ), glutamate, and GABA-A receptors. It has been recognized as early as 1952, that the loss of DHEA/DHEAS in adult life is associated with neuropsychiatric disorders (eg schizophrenia, depression). However, the mechanistic role for DHEA/DHEAS in any of these domains remains speculative, not the least because the presence of these androgens in the adrenal gland and brain is largely confined to humans and only some non-human primates...
December 14, 2018: Journal of Steroid Biochemistry and Molecular Biology
Martin Kaufmann, Corine Martineau, Alice Arabian, Mary Traynor, René St-Arnaud, Glenville Jones
Calcitroic acid, the excretory form of vitamin D, is the terminal product of a 5-step pathway catalyzed by CYP24A1, commencing with C24-hydroxylation of 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3 ). Catabolism of 25-hydroxyvitamin D3 (25-OH-D3 ) proceeds via analogous steps culminating in calcioic acid; however this C23-truncated acid has not been reported in the circulation. It has recently been shown that 24,25-dihydroxyvitamin D3 (24,25-(OH)2 D3 ) is an important factor in optimal bone fracture healing acting via an effector molecule FAM57B2 to produce lactosylceramide...
December 13, 2018: Journal of Steroid Biochemistry and Molecular Biology
Antonio Neme, Sabine Seuter, Marjo Malinen, Tarja Nurmi, Tomi-Pekka Tuomainen, Jyrki K Virtanen, Carsten Carlberg
In the vitamin D intervention study VitDbol (NCT02063334) blood samples were drawn directly before an oral bolus (2000 µg vitamin D3 ) and 24 h later. The focus of phase II of VitDbol was the transcriptome-wide analysis of the effects of vitamin D gene expression in human peripheral blood mononuclear cells (PBMCs). All five participants responded in an individual fashion to the bolus by increases in serum levels of the vitamin D metabolites 25-hydroxyvitamin D3 (25(OH)D3 ) and 1α,25-dihydroxyvitamin D3 (1,25(OH)2 D3 )...
December 8, 2018: Journal of Steroid Biochemistry and Molecular Biology
Madara Ratnadiwakara, Melissa Rooke, Stephen J Ohms, Hugh J French, Rohan B H Williams, Rachel W Li, Donghai Zhang, Robyn M Lucas, Anneke C Blackburn
Breast cancer is a complex disease, and approximately 30% of cases are considered to be hereditary or familial, with a large fraction of this being polygenic. However, it is difficult to demonstrate the functional importance of genes of small effect in population studies, and these genes are not always easily targeted for prevention. The SuprMam (suppressor of mammary tumour) breast cancer susceptibility alleles were previously identified as contributors to spontaneous mammary tumour development in Trp53+/- mice...
December 7, 2018: Journal of Steroid Biochemistry and Molecular Biology
Anastasios Mangelis, Ramona Jühlen, Peter Dieterich, Mirko Peitzsch, Jacques W M Lenders, Stefanie Hahner, Andreas Schirbel, Graeme Eisenhofer
Disorders featuring dysregulated adrenal steroidogenesis, such as primary aldosteronism, can benefit from targeted therapies. The aldosterone and cortisol producing enzymes, aldosterone synthase (CYP11B2) and 11-beta-hydroxylase (CYP11B1), share 93% homology requiring selective drugs for pharmacological treatment. Herein, we introduce an effective in vitro assay for evaluation of steroidogenic enzyme kinetics based on intracellular flux calculations. H295RA cells were cultured in chambers under constant medium flow...
December 6, 2018: Journal of Steroid Biochemistry and Molecular Biology
Z Malihi, Zhenqiang Wu, Carlene M M Lawes, Robert Scragg
In recent years, clinical trials increasingly have given large doses of vitamin D supplements to investigate possible health benefits beyond bone at high 25-hydroxyvitamin D levels. However, there are few publications on the safety of high-dose vitamin D given long term. The study objective was to investigate the cumulative relative risk (RR) of total adverse events, kidney stones, hypercalcemia and hypercalciuria from ≥2800 IU/d vitamin D2 or D3 supplementation, followed for one year or more in randomized controlled trials (RCTs)...
December 6, 2018: Journal of Steroid Biochemistry and Molecular Biology
Nojan Nejatian, Ann-Kathrin Häfner, Firouzeh Shoghi, Klaus Badenhoop, Marissa Penna-Martinez
The arachidonate 5-lipoxygenase (ALOX5) pathway has been implicated in chronic inflammatory disease which may be influenced by vitamin D due to vitamin D response elements (VDRE). We investigated an ALOX5 polymorphism (rs4987105) in patients with type 2 diabetes (T2D) and the in vitro effects of calcitriol (1,25(OH)2 D3 ) on ALOX5 metabolism in monocytes of T2D patients and healthy controls (HC). 533 T2D and 473 HC were genotyped for the rs4987105 polymorphism. In addition, the 25(OH)D3 and 1,25(OH)2 D3 plasma levels were measured in both cohorts...
December 3, 2018: Journal of Steroid Biochemistry and Molecular Biology
Matan Nachliely, Aviram Trachtenberg, Boris Khalfin, Karen Nalbandyan, Merav Cohen-Lahav, Kaori Yasuda, Toshiyuki Sakaki, Andrzej Kutner, Michael Danilenko
Acute myeloid leukemia (AML) is one of the deadliest hematological malignancies without effective treatment for most patients. Vitamin D derivatives (VDDs) - active metabolites 1α,25-dihydroxyvitamin D2 (1,25D2) and 1α,25-dihydroxyvitamin D3 (1,25D3) and their analogs - are differentiation-inducing agents which have potential for the therapy of AML. However, calcemic toxicity of VDDs limits their clinical use at doses effective against cancer cells in vivo. Here, we demonstrate that in AML cell cultures, moderate pro-differentiation effects of low concentrations of VDDs can be synergistically enhanced by structurally distinct compounds known to activate the transcription factor Nuclear Factor (Erythroid-derived 2)-Like 2 (NFE2L2 or Nrf2)...
November 30, 2018: Journal of Steroid Biochemistry and Molecular Biology
Zhenqiang Wu, Carlos A Camargo, John D Sluyter, Kay-Tee Khaw, Zarintaj Malihi, Debbie Waayer, Les Toop, Carlene M M Lawes, Robert Scragg
Chronic pain is a major contributor to the global burden of disability. Prior studies on the association between serum 25-hydroxyvitamin D (25(OH)D) levels and chronic pain have yielded mixed results. The Vitamin D Assessment study, a large randomized controlled trial from New Zealand, offered the opportunity to examine this association in data collected at baseline in all participants, and among those with arthritis or depression. A total of 5110 participants aged 50-84 years were recruited from community general practices...
November 30, 2018: Journal of Steroid Biochemistry and Molecular Biology
X Wang, M Nachliely, J S Harrison, M Danilenko, G P Studzinski
Standard therapy for Acute Myeloid Leukemia (AML) is rarely curative, and several suggested improvements have had little success so far. We have reported that in an in vitro model of a potential therapeutic regimen for AML, the activity of cytarabine (AraC) is enhanced by a sequential treatment with a combination of the vitamin D2 analog Doxercalciferol (D2) and the plant-derived antioxidant carnosic acid (CA) Importantly, the enhancement occurred selectively in patient-derived AML blasts, but not in the normal bone marrow cells...
November 30, 2018: Journal of Steroid Biochemistry and Molecular Biology
Shwe Sin Win, Carlos A Camargo, Kay-Tee Khaw, Carlene M M Lawes, John Sluyter, Debbie Waayer, Les Toop, Robert Scragg
BACKGROUND: Previous studies, mostly with children, have reported inconsistent findings on the associations of vitamin D status with asthma prevalence, exacerbations, and control. Because of limited research with adults, we examined these associations in a large community-based sample of New Zealand adults. METHODS: 5110 participants, aged 50-84 years, were recruited from the community into a clinical trial of vitamin D supplementation. The current analysis is based on baseline blood sample collection to measure serum 25-hydroxyvitamin D (25(OH)D), which was deseasonalized for data analyses; and baseline asthma assessment, which included questions on asthma prevalence, urgent medical care for asthma in the previous 12 months, and control of asthma symptoms in the previous 4 weeks...
November 30, 2018: Journal of Steroid Biochemistry and Molecular Biology
An-Sofie Vanherwegen, Guy Eelen, Gabriela Bomfim Ferreira, Bart Ghesquière, Dana Paulina Cook, Tanja Nikolic, Bart Roep, Peter Carmeliet, Sucheta Telang, Chantal Mathieu, Conny Gysemans
Tolerogenic dendritic cells (tolDCs) instruct regulatory T cells (Tregs) to dampen autoimmunity. Active vitamin D3 (1α,25-dihydroxyvitamin D3 ; 1α,25(OH)2 D3 ) imprints human monocyte-derived DCs with tolerogenic properties by reprogramming their glucose metabolism. Here we identify the glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) as a critical checkpoint and direct transcriptional target of 1α,25(OH)2 D3 in determining the tolDC profile. Using tracer metabolomics, we show that PFKFB4 activity is essential for glucose metabolism, especially for glucose oxidation, which is elevated upon 1α,25(OH)2 D3 exposure...
November 24, 2018: Journal of Steroid Biochemistry and Molecular Biology
Songlin Yu, Weiyan Zhou, Danchen Wang, Yicong Yin, Qian Cheng, Shaowei Xie, Dandan Sun, Honglei Li, Xinqi Cheng, Ling Qiu
This study establishes and validates a rapid method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) without derivatization steps to simultaneously measure of 24,25(OH)2 D2 , 24,25(OH)2 D3 , 25OHD2 , and 25OHD3 , while efficiently separating the 3-epi analogs. Samples were prepared by precipitation and liquid-liquid extraction. The linearity, precision, accuracy, recovery and matrix of the method were thoroughly evaluated according to the Clinical & Laboratory Standards Institute guidelines...
November 23, 2018: Journal of Steroid Biochemistry and Molecular Biology
G D Carter, F Ahmed, J Berry, E Cavalier, R Durazo-Arvizu, E Gunter, G Jones, J Jones, K Phinney, C T Sempos, P J Twomey, E L Williams, S A Wise
The discovery that mutations of the CYP24A1 gene are a cause of idiopathic infantile hypercalcemia (IIH) has revived interest in measuring serum 24,25(OH)2 D3 . Several studies have also suggested that a high 25-hydroxyvitamin D3 (25-OHD3 ):24,25(OH)2 D3 ratio might provide additional diagnostic information in the investigation of vitamin D deficiency. Measurement of 24,25(OH)2 D3 is necessarily restricted to laboratories with mass spectrometry methods although cross reactivity of the metabolite in immunoassays for 25-OHD is a potential cause of misleading results...
November 23, 2018: Journal of Steroid Biochemistry and Molecular Biology
Claire L Greiller, Reetika Suri, David A Jolliffe, Tatiana Kebadze, Aurica G Hirsman, Christopher J Griffiths, Sebastian L Johnston, Adrian R Martineau
Human rhinoviruses commonly cause upper respiratory infections, which may be complicated by secondary bacterial infection. Vitamin D replacement reduces risk of acute respiratory infections in vitamin D-deficient individuals, but the mechanisms by which such protection is mediated are incompletely understood. We therefore conducted experiments to characterise the influence of the major circulating metabolite 25-hydroxyvitamin D (25[OH]D) and the active metabolite 1,25-dihydroxyvitamin D (1,25[OH]2 D) on responses of a respiratory epithelial cell line (A549 cells) to infection with a major group human rhinovirus (RV-16)...
November 23, 2018: Journal of Steroid Biochemistry and Molecular Biology
Björk A, Ribom E, Johansson G, Scragg R, Mellström D, Grundberg E, Ohlsson C, Karlsson M, Ljunggren Ö, Kindmark A
The vitamin D receptor (VDR) has been proposed as a candidate gene for several musculoskeletal phenotypes. However, previous results on the associations between genetic variants of the VDR with muscle strength and falls have been contradictory. The MrOS Sweden survey, a prospective population-based cohort study of 3014 elderly men (mean age 75 years, range 69-81) offered the opportunity to further investigate these associations. At baseline, data were collected on muscle strength and also the prevalence of falls during the previous 12 months...
November 23, 2018: Journal of Steroid Biochemistry and Molecular Biology
P V Ershov, Е O Yablokov, A V Florinskaya, Yu V Mezentsev, L А Kaluzhskiy, A M Tumilovich, А А Gilep, S A Usanov, А S Ivanov
The goal of this work was to test the hypothesis that the affinity of protein-protein interactions in the cytochrome P450-dependent monooxygenase system is modulated by the low-molecular-weight compounds (substrates or inhibitors). The surface plasmon resonance (SPR) based study was carried out using the recombinant protein preparations of three microsomal cytochromes P450 (CYP17A1, CYP21A2, and CYP2C19) and their redox partners: cytochrome b5 (CYB5A), NADPH - cytochrome P450 reductase (CPR), and also iron-sulfur protein adrenodoxin (Adx)...
November 20, 2018: Journal of Steroid Biochemistry and Molecular Biology
Martin Piskacek, Marek Havelka, Kristina Jendruchova, Andrea Knight
In higher metazoans, the nuclear hormone receptors activate transcription trough their specific adaptors, nuclear hormone receptor adaptors NCoA, which are absent in lower metazoans. The Nine amino acid TransActivation Domain, 9aaTAD, was reported for a large number of the transcription activators that recruit general mediators of transcription. In this study, we demonstrated that the 9aaTAD from NHR-49 receptor of nematode C.elegans activates transcription as a small peptide. We showed that the ancient 9aaTAD domains are conserved in the nuclear hormone receptors including human HNF4, RARa, VDR and PPARg...
November 20, 2018: Journal of Steroid Biochemistry and Molecular Biology
Chiara Ricca, Alessia Aillon, Marta Viano, Loredana Bergandi, Elisabetta Aldieri, Francesca Silvagno
Vitamin D and TGF-β exert opposite effects on epithelial-mesenchymal EMT transition. Here we report a novel mechanism of action of TGF-β that promotes the counteracting activity of vitamin D; in two models of human epithelial-mesenchymal EMT transition we demonstrated for the first time that TGF-β strongly induced the expression of vitamin D receptor (VDR) and that 1,25(OH)2 D3 was able to contrast the TGF-β-driven EMT transition by transcriptional modulation. In human bronchial epithelial cells the effects of TGF-β on EMT transition markers (E-Cadherin expression and cell motility) were reversed by pre-treatment and co-treatment with 1,25(OH)2 D3, but not when the hormone was given later...
November 19, 2018: Journal of Steroid Biochemistry and Molecular Biology
Cheryl S Rosenfeld, Paul S Cooke
Estrogen binding to estrogen receptors (ESR) triggers signaling cascades within cells. Historically, a major emphasis has been characterizing estrogen-induced genomic actions resulting from binding to nuclear estrogen receptor 1 (nESR1). However, recent evidence indicates the first receptors estrogens encounter as they enter a cell, membrane ESR1 (mESR1), also play crucial roles. Membrane and nuclear ESR are derived from the same transcripts but the former are directed to the membrane via palmitoylation. Binding and activation of mESR1 leads to rapid fluctuations in cAMP and Ca+2 and stimulation of protein kinase pathways...
November 19, 2018: Journal of Steroid Biochemistry and Molecular Biology
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