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Journal of Steroid Biochemistry and Molecular Biology

Jian Wang, Yan Chen, Ping-Li Mo, Yi-Ju Wei, Kuan-Cheng Liu, Zhan-Guo Zhang, Zhi-Wei Zhang, Xiao-Ping Chen, Lei Zhang
Hepatic progenitor cells (HPCs) might be the origin of hepatocellular carcinoma. 1α, 25-dihydroxyvitamin D3 (1, 25(OH)2 D3 ) (VD3) has been documented as an anticancer agent for various cancers. However, the potential effect of VD3 on the proliferation and malignant transformation of HPCs induced by aflatoxin B1 (AFB1) has not been determined. In this study, we found that AFB1 exhibited the stimulative effects on the proliferation, dedifferentiation and invasion of HPCs via activating AKT pathway but turning off Hippo pathway, which were terminated when VD3 was used in combination with AFB1...
August 9, 2018: Journal of Steroid Biochemistry and Molecular Biology
Lilja Kjalarsdottir, Sarah A Tersey, Mridula Vishwanath, Jen-Chieh Chuang, Bruce A Posner, Raghavendra G Mirmira, Joyce J Repa
AIM: Vitamin D deficiency in rodents negatively affects glucose-stimulated insulin secretion (GSIS) and human epidemiological studies connect poor vitamin D status with type 2 diabetes. Previous studies performed primarily in rat islets have shown that vitamin D can enhance GSIS. However the molecular pathways linking vitamin D and insulin secretion are currently unknown. Therefore, experiments were undertaken to elucidate the transcriptional role(s) of the vitamin D receptor (VDR) in islet function...
July 30, 2018: Journal of Steroid Biochemistry and Molecular Biology
Olivera Bozickovic, Linn Skartveit, Agnete S T Engelsen, Thomas Helland, Kristin Jonsdottir, Marianne Hauglid Flågeng, Ingvild S Fenne, Emiel Janssen, James B Lorens, Lise Bjørkhaug, Jørn V Sagen, Gunnar Mellgren
Steroid receptor coactivator 2 (SRC-2) is a nuclear receptor coactivator, important for the regulation of estrogen receptor alpha (ERα)-mediated transcriptional activity in breast cancer cells. However, the transcriptional role of SRC-2 in breast cancer is still ambiguous. Here we aimed to unravel a more precise transcriptional role of SRC-2 and uncover unique target genes in MCF-7 breast cancer cells, as opposed to the known oncogene SRC-3. Gene expression analyses of cells depleted of either SRC-2 or SRC-3 showed that they transcriptionally regulate mostly separate gene sets...
July 23, 2018: Journal of Steroid Biochemistry and Molecular Biology
Carsten Carlberg, Antonio Neme
The vitamin D-modulated transcriptome of highly responsive human cells, such as THP-1 monocytes, comprises more than 500 genes, half of which are primary targets. Recently, we proposed a chromatin model of vitamin D signaling demonstrating that nearly all vitamin D target genes are located within vitamin D-modulated topologically associated domains (TADs). This model is based on genome-wide binding patterns of the vitamin D receptor (VDR), the pioneer transcription factor PU.1, the chromatin organizer CTCF and histone markers of active promoter regions (H3K4me3) and active chromatin (H3K27ac)...
July 22, 2018: Journal of Steroid Biochemistry and Molecular Biology
Michael E Baker, Richard Lathe
Many actions of estradiol (E2), the principal physiological estrogen in vertebrates, are mediated by estrogen receptor-α (ERα) and ERβ. An important physiological feature of vertebrate ERs is their promiscuous response to several physiological steroids, including estradiol (E2), Δ5 -androstenediol, 5α-androstanediol, and 27-hydroxycholesterol. A novel structural characteristic of Δ5 -androstenediol, 5α-androstanediol, and 27-hydroxycholesterol is the presence of a C19 methyl group, which precludes the presence of an aromatic A ring with a C3 phenolic group that is a defining property of E2...
July 20, 2018: Journal of Steroid Biochemistry and Molecular Biology
Xiaoyan Zhu, Magalie Fréchou, Michael Schumacher, Rachida Guennoun
Treatment with progesterone limits brain damage after stroke. However, the cellular bases of the cerebroprotective effects of progesterone are not well documented. The aims of this study were to determine neural cells and functions that are affected by progesterone treatment and the role of neural progesterone receptors (PR) after stroke. Adult male PRNesCre mice, selectively lacking PR in the central nervous system, and their control PRloxP/loxP littermates were subjected to transient ischemia by middle cerebral artery occlusion (MCAO) for 30 min...
July 19, 2018: Journal of Steroid Biochemistry and Molecular Biology
R Wang, D Tiosano, A Sánchez-Guijo, M F Hartmann, S A Wudy
Growth and development of an embryo or fetus during human pregnancy mainly depend on intact hormone biosynthesis and metabolism in maternal amniotic fluid (AF). We investigated the hormonal milieu in AF and developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of 14 sulfated and 6 unconjugated steroids in AF. 65 A F samples (male: female = 35: 30) of mid-gestation ranging from 16th week of gestation to 25th week of gestation were analyzed. Reference data of 20 steroid levels in AF of healthy women were provided...
July 18, 2018: Journal of Steroid Biochemistry and Molecular Biology
Lucie Zemanová, Hana Navrátilová, Rudolf Andrýs, Kristýna Šperková, Jiří Andrejs, Klára Kozáková, Marc Meier, Gabriele Möller, Eva Novotná, Miroslav Šafr, Jerzy Adamski, Vladimír Wsól
Many enzymes from the short-chain dehydrogenase/reductase superfamily (SDR) have already been well characterized, particularly those that participate in crucial biochemical reactions in the human body (e.g. 11β-hydroxysteroid dehydrogenase 1, 17β-hydroxysteroid dehydrogenase 1 or carbonyl reductase 1). Several other SDR enzymes are completely or almost completely uncharacterized, such as DHRS1 (also known as SDR19C1). Based on our in silico and experimental approaches, DHRS1 is described as a likely monotopic protein that interacts with the membrane of the endoplasmic reticulum...
July 18, 2018: Journal of Steroid Biochemistry and Molecular Biology
Miyu Nishikawa, Kaori Yasuda, Masashi Takamatsu, Keisuke Abe, Kimie Nakagawa, Naoko Tsugawa, Yoshihisa Hirota, Kazuma Tanaka, Shigeaki Yamashita, Shinichi Ikushiro, Tatsuo Suda, Toshio Okano, Toshiyuki Sakaki
We have reported that 25-hydroxyvitamin D3 [25(OH)D3 ] binds to vitamin D receptor and exhibits several biological functions directly in vitro. To evaluate the direct effect of 25(OH)D3 in vivo, we used Cyp27b1 knockout (KO) mice, which had no detectable plasma 1α,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] when fed a diet containing normal Ca and vitamin D. Daily treatment with 25(OH)D3 at 250 μg kg-1  day-1 rescued rachitic phenotypes in the Cyp27b1 KO mice. Bone mineral density, female sexual cycles, and plasma levels of Ca, P, and PTH were all normalized following 25(OH)D3 administration...
July 18, 2018: Journal of Steroid Biochemistry and Molecular Biology
Richard Lathe, Douglas R Houston
Present-day nuclear receptors (NRs) responding to adrenal and sex steroids are key regulators of reproduction and growth in mammals, and are thought to have evolved from an ancestral NR most closely related to extant estrogen-related receptors (ERRs). The molecular events (and ligands) that distinguish steroid-activated NRs (SRs) from their inferred ancestor, that gave rise to both the ERRs and SRs, remain unknown. We report that target sequences for fatty-acylation (palmitoylation) at a key cysteine residue (corresponding to Cys447 in human estrogen receptor ERα) in helix 8 of the ligand-binding domain accurately demarcate SRs from ERRs...
July 17, 2018: Journal of Steroid Biochemistry and Molecular Biology
Masae Horinouchi, Michal Malon, Hiroshi Hirota, Toshiaki Hayashi
Comamonas testosteroni TA441 degrades steroids via 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid, which is presumed to be further degraded by β-oxidation. In the β-oxidation process, Coenzyme A (CoA)-ester of 9-oxo-1,2,3,4,5,6,10,19-octanor-13,17-secoandrost-8(14)-ene-7,17-dioic acid is produced and converted by β-ketoacyl-CoA-transferase encoded by ORF1 and ORF2 (scdL1L2) to cleave the remaining C-ring. In this study, we isolated and identified 4-methyl-5-oxo-octane-1,8-dioic acid and 4-methyl-5-oxo-3-octene-1,8-dioic acid from the culture of the ORF3 (scdN)-null mutant as metabolites of steroid degradation (ADD and cholic acid analogues; cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid)...
July 17, 2018: Journal of Steroid Biochemistry and Molecular Biology
Masae Horinouchi, Hiroyuki Koshino, Michal Malon, Hiroshi Hirota, Toshiaki Hayashi
Comamonas testosteroni TA441 degrades steroid compounds via aromatization of the A-ring to produce 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid (a metabolite with C- and D-rings), which is presumed to be further degraded via β-oxidation. In elucidating the complete steroid degradation process in C. testosteroni, we isolated 9-oxo-1,2,3,4,5,6,10,19-octanor-13,17-secoandrost-8(14)-ene-7,17-dioic acid and several other metabolites containing only C-ring. For conversion of the CoA-ester of this compound, a two-subunit β-ketoacyl-CoA-transferase encoded by ORF1 and ORF2 was shown to be indispensable...
July 16, 2018: Journal of Steroid Biochemistry and Molecular Biology
Dejun Xu, Huanshan He, Xiaohan Jiang, Rongmao Hua, Huali Chen, Li Yang, Jianyong Cheng, Jiaxin Duan, Qingwang Li
SIRT2 has been shown to possess NAD+ -dependent deacetylase and desuccinylase enzymatic activities, it also regulates metabolism homeostasis in mammals. Previous data has suggested that resveratrol, a potential activator of Sirtuins, played a stimulation role in steroidogenesis. Unfortunately, to date, the physiological roles of SIRT2 in ovarian granular cells (GCs) are largely unknown. Here, we studied the function and molecular mechanisms of SIRT2 on steroid hormone synthesis in GCs from Qinchuan cattle. Immunohistochemistry and western blotting showed that SIRT2 was expressed not only in GCs and cumulus cells, but also in oocytes and theca cells...
July 12, 2018: Journal of Steroid Biochemistry and Molecular Biology
Hiroki Mano, Shinichi Ikushiro, Toshiyuki Sakaki
Recently, we successfully generated a novel detection system for vitamin D receptor (VDR) ligands in vivo and in vitro, using a split-luciferase technique called the LucN-LBD-LucC biosensor that is a chimeric fusion protein of firefly luciferase with the ligand binding domain (LBD) of VDR. In this system, the luciferase light intensity of the LucN-LBD-LucC biosensor was decreased by binding of VDR ligands. Although this system is quite useful for evaluation of VDR ligands in a short time, the sensitivity of the LucN-LBD-LucC biosensor is not high enough...
July 9, 2018: Journal of Steroid Biochemistry and Molecular Biology
Lauriane Bonnet, Mohammed Amine Hachemi, Esma Karkeni, Charlene Couturier, Julien Astier, Catherine Defoort, Ljubica Svilar, Jean-Charles Martin, Franck Tourniaire, Jean-François Landrier
Low circulating levels of total and free 25-hydroxyvitamin D (25(OH)D) indicative of vitamin D status have been associated with obesity in humans. Moreover, obesity is thought to play a causal role in the reduction of 25(OH)D levels, and several theories have been put forward to explain this relationship. Here we tested the hypothesis that obesity disrupts vitamin D homeostasis in key organs of vitamin D metabolism. Male C57BL6 mice were fed for 7 or 11 weeks on either a control diet (control, 10% energy from fat) or a high-fat diet (HF, 60% energy from fat) formulated to provide equivalent vitamin D3 intake in both groups...
July 7, 2018: Journal of Steroid Biochemistry and Molecular Biology
Eduardo Cruz-Ramos, Antonio Sandoval-Hernández, Angeles C Tecalco-Cruz
Chromosome region maintenance 1 (CRM-1) and calreticulin (CALR) are two proteins that act as exportins for some nuclear receptors, in addition to other critical functions for cellular homeostasis. In several cancer types, CRM-1 and CALR are upregulated suggesting an imbalance in their functions. However, the regulation of CRM-1 and CALR, and their biological implications, are not completely known. Here, we evaluated the interplay between the levels of CRM-1 and CALR, and estrogen receptor alpha (ERα) status, in breast cancer cells...
July 5, 2018: Journal of Steroid Biochemistry and Molecular Biology
Gemma Ferrer-Mayorga, María Jesús Larriba, Piero Crespo, Alberto Muñoz
Colorectal cancer (CRC) is the neoplasia that is most frequently associated with vitamin D deficiency in epidemiological and observational studies in terms of incidence and mortality. Many mechanistic studies show that the active vitamin D metabolite (1α,25-dihydroxyvitamin D3 or calcitriol) inhibits proliferation and promotes epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptor (VDR) via the regulation of a high number of genes. A key action underlining this effect is the multilevel inhibition of the Wnt/β-catenin signaling pathway, whose abnormal activation in colon epithelial cells initiates and promotes CRC...
July 4, 2018: Journal of Steroid Biochemistry and Molecular Biology
Wanda Sicinska, Dominik Gront, Kamil Sicinski
The mechanism through which nuclear receptors respond differentially to structurally distinct agonists is a poorly understood process. We present a computational method that identifies nuclear receptor amino acids that are likely involved in biological responses triggered by ligand binding. The method involves tracing how structural changes spread from the ligand binding pocket to the sites on the receptor surface, which makes it a good tool for studying allosteric effects. We employ the method to the vitamin D receptor and verify that the identified amino acids are biologically relevant using a broad range of experimental data and a genome browser...
June 30, 2018: Journal of Steroid Biochemistry and Molecular Biology
Hui-Chen Wang, Wen-Sen Lee
It has been reported that progesterone (P4) can contribute to the aggressiveness of human breast cancers through promoting cytoplasmic localization of p27 and stimulating proliferation. However, the molecular mechanisms underlying P4-induced cytoplasmic retention of p27 are still unclear. Here, we demonstrated that P4 (12.5-100 nM) concentration-dependently increased the number of T47D and MCF-7 cells. P4 (50 nM) also time-dependently increased the levels of p27 protein. Knock-down of p27 using the small interfering RNA (siRNA) technique abolished the P4-increased cell number of T47D and MCF-7...
June 27, 2018: Journal of Steroid Biochemistry and Molecular Biology
Krzysztof Wycisk, Aneta Tarczewska, Magdalena Kaus-Drobek, Michał Dadlez, Rafał Hołubowicz, Zbigniew Pietras, Andrzej Dziembowski, Michał Taube, Maciej Kozak, Marek Orłowski, Andrzej Ożyhar
Nuclear receptors (NRs) are a family of ligand-dependent transcription factors activated by lipophilic compounds. NRs share a common structure comprising three domains: a variable N-terminal domain (NTD), a highly conserved globular DNA-binding domain and a ligand-binding domain. There are numerous papers describing the molecular details of the latter two globular domains. However, very little is known about the structure-function relationship of the NTD, especially as an intrinsically disordered fragment of NRs that may influence the molecular properties and, in turn, the function of globular domains...
June 23, 2018: Journal of Steroid Biochemistry and Molecular Biology
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