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Jennifer R Rainville, Grant L Weiss, Nathan Evanson, James P Herman, Nandini Vasudevan, Jeffrey G Tasker
Glucocorticoid binding to the intracellular glucocorticoid receptor (GR) stimulates the translocation of the GR from the cytosol to the nucleus, which leads to the transactivation or transrepression of gene transcription. However, multiple lines of evidence suggest that glucocorticoid signaling can also be initiated from the plasma membrane. Here, we provide evidence for membrane-initiated glucocorticoid signaling by a membrane-impermeant dexamethasone-bovine serum albumin (Dex-BSA) conjugate, which induced GR nuclear trafficking in hypothalamic neurons in vitro and in vivo...
December 11, 2017: Steroids
Niels Asmussen, Zhao Lin, Michael J McClure, Zvi Schwartz, Barbara D Boyan
Endochondral bone formation is a precise and highly ordered process whose exact regulatory framework is still being elucidated. Multiple regulatory pathways are known to be involved. In some cases, regulation impacts gene expression, resulting in changes in chondrocyte phenotypic expression and extracellular matrix synthesis. Rapid regulatory mechanisms are also involved, resulting in release of enzymes, factors and micro RNAs stored in extracellular matrisomes called matrix vesicles. Vitamin D metabolites modulate endochondral development via both genomic and rapid membrane-associated signaling pathways...
December 9, 2017: Steroids
Sofija S Bekić, Maja A Marinović, Edward T Petri, Marija N Sakač, Andrea R Nikolić, Vesna V Kojić, Andjelka S Ćelić
Synthesis and biological evaluation of steroidal derivatives with anticancer properties is an active area of drug discovery. Here we measured the relative affinities of D-seco modified steroidal derivatives for estrogen receptor α, estrogen receptor β or androgen receptor ligand binding domains using an optimized non-transcriptional fluorescent cell assay in yeast. Ligand binding domains of steroid receptors were expressed in-frame with yellow fluorescent protein in the yeast Sacharomyces cerevisiae. Addition of known steroid ligands to yeast expressing the appropriate cognate receptor results in increased fluorescence intensity, enabling estimation of receptor binding affinities in a dose-response and time-dependent manner...
December 7, 2017: Steroids
Xiaoyan Pang, Xiuping Lin, Junfeng Wang, Rui Liang, Yongqi Tian, Limbadri Salendra, Xiaowei Luo, Xuefeng Zhou, Bin Yang, Zhengchao Tu, Yonghong Liu
Three new highly oxygenated sterols (1-3) and a new dihydroisocoumarin (7) together with six known compounds were isolated from the extracts of the culture of a sponge-derived fungus Cladosporium sp. SCSIO41007. The structures of all new compounds (1-3, 7) were determined by the extensive spectroscopic analysis including NMR, MS, IR, and UV. Their absolute configurations were determined by X-ray single-crystal and CD data analysis. Compound 2 exhibited weak inhibitory activity against H3N2 with the IC50 value of 16...
December 6, 2017: Steroids
Lillian R Sturmer, Dylan Dodd, Christina S Chao, Run-Zhang Shi
BACKGROUND: Late night salivary cortisol measurement is a clinically important and convenient screening test for Cushing's syndrome. Tandem mass spectrometry (LC-MS/MS) assays have superior sensitivity and specificity compared to immunoassays. Our goal was to improve a LC-MS/MS method to measure salivary cortisol in both adult and pediatric patients and to characterize its analytical performance by method validation and clinical performance by chart review. METHODS: We improved a LC-MS/MS method originally developed for urine cortisol to measure low level salivary cortisol...
November 29, 2017: Steroids
Katherine R Tonn Eisinger, Erin B Larson, Marissa I Boulware, Mark J Thomas, Paul G Mermelstein
Within the adult female, estrogen signaling is well-described as an integral component of the physiologically significant hypothalamic-pituitary-gonadal axis. In rodents, the timing of ovulation is intrinsically entwined with the display of sexual receptivity. For decades, the importance of estradiol activating intracellular estrogen receptors within the hypothalamus and midbrain/spinal cord lordosis circuits has been appreciated. These signaling pathways primarily account for the ability of the female to reproduce...
November 28, 2017: Steroids
Vladimir A Zolottsev, Yaroslav V Tkachev, Alexandra S Latysheva, Vladimir A Kostin, Roman A Novikov, Vladimir P Timofeev, Galina E Morozevich, Alexey V Kuzikov, Victoria V Shumyantseva, Alexander Y Misharin
Four new 4,5-dihydro-1,3-oxazole, and four new benzo-[d]-oxazole derivatives of [17(20)E]-21-norpregnene, differing in the structure of steroid moiety, were synthesized and evaluated for their potency to inhibit 17α-hydroxylase/17,20-lyase (CYP17A1) activity. Among new compounds, the only oxazolinyl derivative comprising 5-oxo-4,5-seco-3-yn- moiety potently inhibited CYP17A1. Binding modes of the oxazolinyl derivatives of [17(20)E]-21-norpregnene were analyzed by molecular dynamics simulations, and model of alternate, water-bridged type II interaction was proposed for these compounds...
November 25, 2017: Steroids
H M Rivera, T L Stincic
This review lays out the evidence for the role of E2 in homeostatic and hedonic feeding across several species. While significant effort has been expended on homeostatic feeding research, more studies for hedonic feeding need to be conducted (i.e. are there increases in meal size and enhanced motivation to natural food rewards). By identifying the underlying neural circuitry involved, one can better delineate the mechanisms by which E2 influences feeding behavior. By utilizing more selective neural targeting techniques, such as optogenetics, significant progress can be made toward this goal...
November 24, 2017: Steroids
Emil Yu Yamansarov, Dmitri V Kazakov, Natal'ya I Medvedeva, Elmira F Khusnutdinova, Oxana B Kazakova, Yuliya V Legostaeva, Gumer Yu Ishmuratov, Le Mai Huong, Tran Thi Hong Ha, Do Thi Huong, Kyrill Yu Suponitsky
A series of new steroidal peroxides - 3'-trifluoromethylated 1,2,4-trioxolanes and 1,2,4,5-tetraoxanes based on deoxycholic acid were prepared via the reactions of the Griesbaum coozonolysis and peroxycondensation, respectively. 1,2,4-Trioxolanes were synthesized by the interaction of methyl O-methyl-3-oximino-12α-acetoxy-deoxycholate with CF3C(O)CH3 or CF3C(O)Ph and O3 as the mixtures of four possible stereoisomers at ratios of 1:2:2:1 and in yields of 50% and 38%, respectively. The major diastereomer of methyl 12α-acetoxy-5β-cholan-24-oate-3-spiro-5'-(3'-methyl-3'-trifluoromethyl-1',2',4'-trioxolane) was isolated via crystallization of a mixture of stereoisomers from hexane and its (3S,3'R)-configuration was determined using X-ray crystallographic analysis...
November 24, 2017: Steroids
Hannah Weber, Michael J Garabedian
Mediator is a conserved, multi-subunit macromolecular machine divided structurally into head, middle, and tail modules, along with a transiently associating kinase module. Mediator functions as an integrator of transcriptional regulatory activity by interacting with DNA-bound transcription factors and with RNA polymerase II (Pol II) to both activate and repress gene expression. Mediator has been shown to affect multiple steps in transcription, including chromatin looping between enhancers and promoters, pre-initiation complex formation, transcriptional elongation, and mRNA splicing...
November 17, 2017: Steroids
Yan Li, Jiafeng Yuan, Qianwen Wang, Lijie Sun, Yunying Sha, Yanxiang Li, Lizhong Wang, Zhonghua Wang, Yonggang Ma, Hui Cao
1, 25-dihydroxyvitamin D3 (1, 25 (OH)2 D3) and mechanical stimuli in physiological environment contributes greatly to osteoporosis pathogenesis. Wide investigations have been conducted on how 1, 25-dihydroxyvitamin D3 and mechanical stimuli separately impact osteoblasts. This study reports the collective influences of 1, 25-dihydroxyvitamin D3 and flow shear stress (FSS) on biological functions of osteoblasts. 1, 25 (OH)2 D3 were prepared in various kinds of concentrations (0, 1, 10, 100 nmmol/L), while physiological fluid shear stress (12 dynes/cm(2)) was produced by using a parallel-plate fluid flow system...
November 16, 2017: Steroids
Irina Lerman, Stephen R Hammes
Myeloid cell production within the bone marrow is accelerated in the setting of cancer, and the numbers of circulating and infiltrating neutrophils and granulocytic myeloid derived suppressor cells (MDSCs) correlate with tumor progression and patient survival. Cancer is therefore able to hijack the normally host-protective immune system and use it to further fuel growth and metastasis. Myeloid cells secrete neutrophil elastase and neutrophil extracellular traps (NETs) in response to cues within the tumor microenvironment, thereby leading to enhanced activity in a variety of cancer types...
November 16, 2017: Steroids
Sandi R Wilkenfeld, Chenchu Lin, Daniel E Frigo
Steroid hormones are lipophilic molecules produced in one cell that can travel great distances within the body to elicit biological effects in another cell. In the canonical pathway, steroid hormone binding to a nuclear receptor (NR), often in the cytoplasm, causes the receptor to undergo a conformational change and translocate to the nucleus, where it interacts with specific sequences of DNA to regulate transcription. In addition to the classical genomic mechanism of action, alternate mechanisms of steroid activity have emerged that involve rapid, non-genomic signaling...
November 16, 2017: Steroids
Ellis R Levin
Estrogen receptors (ER) alpha and beta as well as many other steroid receptors are found both within the nucleus and outside the nucleus. This includes extra-nuclear receptors in many organelles, including mitochondria, endoplasmic reticulum, cytosolic endosomes, and membrane lipid rafts, such as caveolae. The functions of these receptors in the various extra-nuclear cell organelles are not well described, but progress for understanding steroid receptor signaling from the membrane has advanced. In this Review I will discuss the enlarging role of membrane ER signaling to the expression, cell localization, and function of transcription factors that are essential to mediate cell physiology or pathophysiology in many organs...
November 16, 2017: Steroids
D Joshua Cohen, Vaidehi Patel, Anjali Verma, Barbara D Boyan, Zvi Schwartz
17β-Estradiol (E2) promotes metastasis of triple negative breast cancer cells to bone. Recent studies show many triple negative breast cancer cell lines lacking the 66 kDa estrogen receptor (ER) alpha (ERα66) or its splice variant ERα46, express another splice variant, ERα36 associated with membrane-mediated rapid actions of the hormone. qPCR and western blot confirmed that MCF7 cells possessed ERα splice variants ERα66, ERα46 and ERα36, while ER-negative breast cancer cells MDA-MB-231 possessed only ERα36...
November 10, 2017: Steroids
Roberta de Souza Santos, Aaron P Frank, Deborah J Clegg
The influence of sex on cellular function and metabolism is often ill defined in many human and animal studies. The National Institute of Health (NIH) recognized this gap in scientific knowledge and mandated that sex be factored into the design and data analysis of all cell culture and animal studies. Therefore, it is critical to understand how to incorporate sex in pre-clinical and clinical research. Here, we discuss how the sexual identify of cells influences experimental responses in cell culture and we highlight the importance of the culture media and its constituents to the function of cells...
November 10, 2017: Steroids
Rania S Sulaiman, Mahita Kadmiel, John A Cidlowski
Glucocorticoids (GCs) are essential steroid hormones that regulate numerous metabolic and homeostatic functions in almost all physiological systems. Synthetic glucocorticoids are among the most commonly prescribed drugs for the treatment of various conditions including autoimmune, allergic and inflammatory diseases. Glucocorticoids are mainly used for their potent anti-inflammatory and immunosuppressive activities mediated through signal transduction by their nuclear receptor, the glucocorticoid receptor (GR)...
November 9, 2017: Steroids
Weihui Yuan, Junhui Guo, Xude Wang, Guangyue Su, Yuqing Zhao
As active components of ginseng, 25-methoxylprotopanaxadiol and 25-hydroxyprotopanaxadiol exhibited an ability to inhibit the growth and proliferation or to induce the differentiation and apoptosis of tumour cells. We modified 25-OCH3-PPD and 25-OH-PPD with non-protein amino acids and a series of derivatives was obtained by chromatographic separation, purification and spectroscopy analysis. Thirteen derivatives of 25-OCH3-PPD (compounds 1-13) and 12 derivatives of 25-OH-PPD (compounds 14-25) were synthesised...
November 9, 2017: Steroids
Derek A Schreihofer, Phong Duong, Rebecca L Cunningham
Sex steroid receptors act as ligand activated nuclear transcription factors throughout the body, including the brain. However, post-translational modification of these receptors can direct them to extranuclear sites, including the plasma membrane, where they are able to initiate rapid signaling. Because of the conserved domain structure of these receptors, alternative exon splicing can result in proteins with altered nuclear and extranuclear actions. Although much attention has focused on internal and C-terminal splice variants, both estrogen and androgen receptors undergo N-terminal truncations, as well...
November 9, 2017: Steroids
Tong Woei Yenn, Muhammad Arslan Khan, Nur Amiera Syuhada, Leong Chean Ring, Darah Ibrahim, Wen-Nee Tan
The emergence of beta lactamase producing bacterial strains eliminated the use of beta lactam antibiotics as chemotherapeutic alternative. Beta lactam antibiotics can be coupled with non-antibiotic adjuvants to combat these multidrug resistant strains. We study the synergistic antibiotic effect of stigmasterol as adjuvant of ampicillin against clinical isolates. Ampicillin was used in this study as a beta lactam antibiotic model. All test bacteria were beta lactamase producing clinical isolates. The combination showed significantly better antibiotic activity on all bacteria tested...
November 7, 2017: Steroids
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