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Journal of Steroid Biochemistry and Molecular Biology

Valentin Trujillo, Paulina Marín-Luevano, Irma González-Curiel, Adrián Rodríguez-Carlos, Maira Ramírez-Reyes, Esther Layseca-Espinosa, José A Enciso-Moreno, Lorenza Díaz, Bruno Rivas-Santiago
Foot ulceration is one of the most common and complex sequelae of diabetes mellitus, generally posing a therapeutic challenge due to poor healing responses and high rates of complications, including peripheral vascular disease, ischemia and infections. Calcitriol, the most active vitamin D metabolite, induces antimicrobial peptides production in keratinocytes from diabetic foot ulcers (DFU); however, little is known about its effects on angiogenic factors in this pathology. Herein we aimed at studying whether calcitriol induces angiogenic molecules in keratinocytes under normoxic and hypoxic conditions, and if these molecules are able to improve cell migration in vitro...
October 14, 2017: Journal of Steroid Biochemistry and Molecular Biology
Jiarong Li, Milton Mihalcioiu, Lifeng Li, Mahvash Zakikhani, Anne Camirand, Richard Kremer
Vitamin D plays an important role in regulation of skeletal muscle tone and contraction. Serum vitamin D status is linked to muscle power and force in adolescent girls, and vitamin D deficiency is associated with myopathies in children and poorer physical performance in the elderly. We previously reported that vitamin D deficiency is linked to a significant increase in muscle fatty infiltration in healthy young women, and studies in patients with neuromuscular disorders also associate muscle weakening and lipid content...
October 13, 2017: Journal of Steroid Biochemistry and Molecular Biology
Benedito de Sousa Almeida-Filho, Heloisa De Luca Vespoli, Eduardo Carvalho Pessoa, Murilo Machado, Jorge Nahas-Neto, Eliana Aguiar Petri Nahas
This study aimed to evaluate the association between pretreatment vitamin D (VD) deficiency with breast cancer prognostic features in Brazilian postmenopausal women. An analytical cross sectional study was conducted with 192 women, aged 45-75 years, attended at University Hospital. Women with recent diagnosis of breast cancer, in amenorrhea >12months and age ≥45 years, without medication use or clinical conditions that interfere with VD values were included. Clinical and anthropometric data were collected...
October 11, 2017: Journal of Steroid Biochemistry and Molecular Biology
Jenny H Pham, Catherine M Will, Vance L Mack, Matthew Halbert, Edward Alexander Conner, Kevin M Bucholtz, James L Thomas
3β-hydroxysteroid dehydrogenase type 1 (3β-HSD1) is selectively expressed in human placenta, mammary glands and breast tumors in women. Human 3β-HSD2 is selectively expressed in adrenal glands and ovaries. Based on AutoDock 3 and 4 results, we have exploited key differences in the amino acid sequences of 3β-HSD1 (Ser194, Arg195) and 3β-HSD2 (Gly194, Pro195) by designing a selective inhibitor of 3β-HSD1. 2,16-Dicyano-4,5-epoxy-androstane-3,17-dione (16-cyano-17-keto-trilostane or DiCN-AND) was synthesized in a 4-step procedure from androstenedione...
October 11, 2017: Journal of Steroid Biochemistry and Molecular Biology
Aishah Alhodhodi, Hanaa Alkharobi, Matthew Humphries, Hasanain Alkhafaji, Reem El-Gendy, Georg Feichtinger, Valerie Speirs, James Beattie
Estradiol (E2) has many important actions in the tissues of the oral cavity. Disruption of E2 metabolism or alterations in systemic E2 concentrations have been associated with compromised periodontal health. In many instances such changes occur secondarily to the well characterised effects of E2 on bone physiology -especially maintenance of bone mineral density (BMD). Despite these important epidemiological findings, little is known about the mechanism of action of E2 in oral tissues or the expression and function of oestrogen receptor (ER) isoforms in these tissues...
October 11, 2017: Journal of Steroid Biochemistry and Molecular Biology
David O Rees, Peter J Crick, Gareth J Jenkins, Yuqin Wang, William J Griffiths, Tim H Brown, Bilal Al-Sarireh
Bile acids have been implicated in the development of gastrointestinal malignancies. Both the specific nature of individual bile acids and their concentration appear key factors in the carcinogenic potency of bile. Using liquid chromatography mass spectrometry (LC-MS) we performed quantitative profiling of bile extracted directly from the common bile duct in 30 patients (15 patients with pancreatic cancer and 15 patients with benign disease). Separation and detection of bile acids was performed using a 1.7μm particle size reversed-phase C18 LC column at a flow rate of 200μL/min with negative electrospray ionization MS...
October 11, 2017: Journal of Steroid Biochemistry and Molecular Biology
M H Blokland, E F van Tricht, L A van Ginkel, S S Sterk
A robust LC-MS/MS method was developed to quantify a large number of phase I and phase II steroids in urine. The decision limit is for most compounds lower than 1ngml(-1) with a measurement uncertainty smaller than 30%. The method is fully validated and was applied to assess the influence of administered synthetic steroids and beta-agonists on the steroidogenesis. From three animal experiments, clenbuterol, diethylstilbestrol and stanozolol, the steroid profiles in urine of bovine animals were compared before and after treatment...
October 10, 2017: Journal of Steroid Biochemistry and Molecular Biology
Rui Wang, Dong Gao, Yin Zhou, Lu Chen, Bin Luo, Yanrong Yu, Hao Li, Jiawei Hu, Qiren Huang, Ming He, Weijie Peng, Dan Luo
Diabetic Mellitus is a risk factor for osteoporosis. It has been suggested that altered estrogen or estrogen receptor α/β (ERα/β) signaling may be involved in diabetic osteoporosis. The present study is to investigate the effects of high glucose on ERα/β signaling in osteoblastic MC3T3-E1 and how the altered signaling of ERα/β affect osteoblastic bone formation. ERα/β signaling was demonstrated as ERα/β protein expression (Western Blotting) and ER transcription activity (Luciferase Reporter assays)...
October 10, 2017: Journal of Steroid Biochemistry and Molecular Biology
G Schuler, A Sánchez-Guijo, M F Hartmann, S A Wudy
Sulfonated steroids (s-St) have been usually regarded as inactive metabolites but are progressively considered as precursors for the intra-tissue formation of bioactive steroids. Moreover, independent effects without preceding removal of the sulfate group have been observed. We use the porcine testicular-epididymal compartment as a model to investigate the still largely unknown s-St physiology as the boar exhibits an intriguingly broad s-St spectrum predominantly originating from the testis. The application of LC-MS/MS in steroidomics enables the determination of unconjugated and intact sulfonated steroids with currently highest specificity and good sensitivity, allowing the concurrent measuring of numerous analytes in larger quantities of samples...
October 10, 2017: Journal of Steroid Biochemistry and Molecular Biology
D Fietz
In various tissues, steroid hormones may be sulfated, glucuronidated or otherwise modified. For a long time, these hydrophilic molecules have been considered to be merely inactive metabolites for excretion via bile or urine. Nevertheless, different organs such as the placenta and breast tissue produce large amounts of sulfated steroids. After the discovery of the enzyme steroid sulfatase, which is able to re-activate sulfated steroids, these precursor molecules entered the focus of interest again as a local supply for steroid hormone synthesis with a prolonged half-life compared to their unconjugated counterparts...
October 7, 2017: Journal of Steroid Biochemistry and Molecular Biology
Dimitrios Papadopoulos, Mazen Shihan, Georgios Scheiner-Bobis
In the spermatogenic cell line GC-2, dehydroepiandrosterone sulfate (DHEAS), activates the Src/Ras/c-Raf/Erk1/2/CREB(ATF-1) signaling cascade. Since DHEAS is present in the gonads, and since spermatogenesis and maturation of spermatogonia to haploid spermatozoa requires activation of Erk1/2, the triggering of these signaling events by DHEAS might have physiological relevance. In the Sertoli cell line TM4, DHEAS-induces activation of Erk1/2, CREB, and ATF-1, stimulates expression of claudin-3 and claudin-5 and augments transepithelial resistance, indicating the formation of tight junctions between adjacent Sertoli cells...
October 7, 2017: Journal of Steroid Biochemistry and Molecular Biology
Keisha Harrison, Stephanie Sisley
Vitamin D deficiency is linked to type 2 diabetes and we recently showed this may be through action of vitamin D in the paraventricular nuclei (PVN) in the hypothalamus of the brain. This review focuses on the known roles of the PVN in glucose control and how previously discovered actions of vitamin D in other tissues may translate to action in the PVN. Specifically, we focus on the role of insulin and inflammation in the hypothalamus and how these may be modified through vitamin D action.
October 6, 2017: Journal of Steroid Biochemistry and Molecular Biology
Iltaf Shah, M Kalim Akhtar, Soleiman Hisaindee, Muhammad A Rauf, Mohammed Sadig, S Salman Ashraf
Vitamin D deficiency has been implicated in a plethora of diseases including rheumatoid arthritis, Parkinson's disease, Alzheimer's disease, and osteoporosis. Deficiency of this vitamin is a global epidemic affecting both developing and developed nations. Within a clinical context, the qualitative and quantitative analysis of vitamin D is therefore vital. The main metabolic markers for assessing vitamin D status in humans are the hydroxylated forms of vitamin D, 25OHD3 and 25OHD2 on account of their long half-lives within the body and excellent stability...
October 5, 2017: Journal of Steroid Biochemistry and Molecular Biology
Nadhir Litim, Marc Morissette, Donatella Caruso, Roberto C Melcangi, Thérèse Di Paolo
Dutasteride is a 5alpha-reductase inhibitor in clinical use to treat endocrine conditions. The present study investigated the neuroprotective mechanisms of action of dutasteride in intact and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mice using a low dose of MPTP not affecting motor activity modeling early stages of Parkinson's disease (PD). We hypothesized that dutasteride neuroprotection is due to altered steroids levels. Dutasteride pre-treatment prevented loss of striatal dopamine (DA) and its metabolite DOPAC...
October 2, 2017: Journal of Steroid Biochemistry and Molecular Biology
Annekathrin M Keiler, Dana Macejova, Birgit M Dietz, Judy L Bolton, Guido F Pauli, Shao-Nong Chen, Richard B van Breemen, Dejan Nikolic, Florian Goerl, Michael H Muders, Oliver Zierau, Günter Vollmer
Supplements with estrogenic activities are intensively investigated as potential alternatives for the treatment of menopausal symptoms. These investigations include studies on their safety regarding potential breast cancer risks. Therefore, the aim of this study was to assess whether or not a standardized hops (Humulus lupulus) extract, containing 0.42% of the estrogenic flavanone, 8-prenylnaringenin, would stimulate growth of methyl-nitrosourea (MNU) induced mammary cancer in ovariectomized (OVX) Sprague-Dawley (SD) rats or would impact on the proliferative activity within the normal mammary gland of Wistar rats...
September 27, 2017: Journal of Steroid Biochemistry and Molecular Biology
Yu H Zhong, Jasbeer Dhawan, Joel A Kovoor, John Sullivan, Wei X Zhang, Dennis Choi, Anat Biegon
Accumulating evidence suggests that expression of aromatase, the enzyme responsible for the conversion of androgens to estrogens, is transiently upregulated in rat stroke models. It was further suggested that increased aromatase expression is linked to neuroinflammation and that it is neuroprotective in females. Our goal was to investigate aromatase upregulation in male rats subjected to experimental stroke in in relationship to neuroinflammation, infarct and response to treatment with different putative neuroprotective agents...
September 27, 2017: Journal of Steroid Biochemistry and Molecular Biology
S A Wudy, G Schuler, A Sánchez-Guijo, M F Hartmann
Steroids are small and highly important structural or signalling molecules in living organisms and their metabolism is complex. Due to the multiplicity of enzymes involved there are many different steroid related disorders. E.g., an individual enzyme defect is rather rare but can share various clinical symptoms and can thus be hardly diagnosed clinically. Therefore, reliable hormonal determination still presents the most reasonable initial diagnostic approach and helps to avoid uncritical and expensive attempts at molecular diagnostic testing...
September 26, 2017: Journal of Steroid Biochemistry and Molecular Biology
Ali S Alzahrani, Meshael Alswailem, A K Murugan, Doha Al-Humaida, Cameron P Capper, Richard J Auchus, Ebtesam Qasem, Ohoud Alzahrani, Afaf Al-Sagheir, Bassam Ben Abbas
Despite ethnic variation, 11 β-hydroxylase deficiency (11-β OHD) has generally been considered the second most common subtype of congenital adrenal hyperplasia (CAH). We report a high rate of novel mutations in this gene from Saudi Arabia. We studied 16 patients with 11-β OHD from 8 unrelated families. DNA was isolated from peripheral blood. The 9 exons and exon-intron boundaries of CYP11B1 were PCR-amplified and directly sequenced. The novel mutations were functionally characterized using subcloning, in vitro mutagenesis, cell transfection and 11-deoxycortisol: cortisol conversion assays...
September 26, 2017: Journal of Steroid Biochemistry and Molecular Biology
Gary Grosser, Josefine Bennien, Alberto Sánchez-Guijo, Katharina Bakhaus, Barbara Döring, Michaela Hartmann, Stefan A Wudy, Joachim Geyer
The sodium-dependent organic anion transporter SOAT/Soat shows highly specific transport activity for sulfated steroids. SOAT substrates identified so far include dehydroepiandrosterone sulfate, 16α-hydroxydehydroepiandrosterone sulfate, estrone-3-sulfate, pregnenolone sulfate, 17β-estradiol-3-sulfate, and androstenediol sulfate. Apart from these compounds, many other sulfated steroids occur in mammals. Therefore, we aimed to expand the substrate spectrum of SOAT and analyzed the SOAT-mediated transport of eight different sulfated steroids by combining in vitro transport experiments in SOAT-transfected HEK293 cells with LC-MS/MS analytics of cell lysates...
September 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
Jisu Oh, Amy E Riek, Rong M Zhang, Samantha A S Williams, Isra Darwech, Carlos Bernal-Mizrachi
The c-Jun N-terminal kinase 2 (JNK2) signaling pathway contributes to inflammation and plays a key role in the development of obesity-induced insulin resistance and cardiovascular disease. Macrophages are key cells implicated in these metabolic abnormalities. Active vitamin D downregulates macrophage JNK activation, suppressing oxidized LDL cholesterol uptake and foam cell formation and promoting an anti-inflammatory phenotype. To determine whether deletion of JNK2 prevents high blood pressure and atherosclerosis known to be induced by vitamin D deficiency in mice, we generated mice with knockout of JNK2 in a background susceptible to diet-induced atherosclerosis (LDLR(-/-))...
September 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
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