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Journal of Steroid Biochemistry and Molecular Biology

Marketa Smidkova, Miroslav Hajek, Santosh Kumar Adla, Barbora Slavikova, Hana Chodounska, Marika Matousova, Helena Mertlikova-Kaiserova, Eva Kudova
A broad variety of central nervous system diseases have been associated with glutamate induced excitotoxicity under pathological conditions. The neuroprotective effects of neurosteroids can combat this excitotoxicity. Herein, we have demonstrated the neuroprotective effect of novel steroidal N-methyl-D-aspartate receptor inhibitors against glutamate- or NMDA- induced excitotoxicity. Pretreatment with neurosteroids significantly reduced acute L-glutamic acid or NMDA excitotoxicity mediated by Ca2+ entry and consequent ROS (reactive oxygen species) release and caspase-3 activation...
March 11, 2019: Journal of Steroid Biochemistry and Molecular Biology
Michele V Clarke, Patricia K Russell, Jeffrey D Zajac, Rachel A Davey
We have previously shown that expression of the androgen receptor (AR) in neurons within the brain positively regulates hind-limb muscle mass and physical activity in male mice. To further investigate the region of the brain responsible for mediating these effects of testosterone and to determine whether they are only important for muscle mass accrual during development or whether they are also important for the maintenance of muscle mass in the adult, we deleted the AR specifically in the hypothalamus of adult male mice (Hyp-ARKOs)...
March 7, 2019: Journal of Steroid Biochemistry and Molecular Biology
Stefan Poschner, Alexandra Maier-Salamon, Theresia Thalhammer, Walter Jäger
Polyphenols in foods and dietary supplements are commonly used for the prevention and treatment of a variety of malignancies, including breast cancer. However, daily intake by patients with breast cancer is controversial, as these compounds may stimulate cancer growth. Estrogens serve key roles in breast cancer cell proliferation; therefore, understanding the interaction between endogenous steroid hormones and natural dietary polyphenols is essential. Currently, comprehensive knowledge regarding these effects remains limited...
March 6, 2019: Journal of Steroid Biochemistry and Molecular Biology
Martiniano Bello, David Méndez-Luna, Viviana Sarmiento, José Correa Basurto, Nayelli Najera, Francisco Villarreal, Guillermo Ceballos
(-)-Epicatechin (Epi) has been demonstrated to activate pathways involved in GPER-stimulated nitric oxide (NO) production via endothelial NO synthase, known as the eNOS/NO pathway. Previous studies combining synthesis of four Epi derivatives demonstrated that Epi and Epi-prop, Epi-4-prop and Epi-5-prop were able to bind GPER by acting as GPER agonists, whereas docking studies allowed observation of structural details of the binding of these derivatives at the GPER binding site. However, due to the nature of past studies, the theoretical methods employed did not allow observation of structural and energetic details linked to ligand binding at the GPER binding site...
March 6, 2019: Journal of Steroid Biochemistry and Molecular Biology
Priya Bhardwaj, CheukMan C Au, Alberto Benito-Martin, Heta Ladumor, Sofya Oshchepkova, Ruth Moges, Kristy A Brown
Obesity is a risk factor for estrogen receptor-positive (ER+) breast cancer after menopause. The pro-proliferative effects of estrogens are well characterized and there is a growing body of evidence to also suggest an important role in tumorigenesis. Importantly, obesity not only increases the risk of breast cancer, but it also increases the risk of recurrence and cancer-associated death. Aromatase is the rate-limiting enzyme in estrogen biosynthesis and its expression in breast adipose stromal cells is hypothesized to drive the growth of breast tumors and confer resistance to endocrine therapy in obese postmenopausal women...
March 6, 2019: Journal of Steroid Biochemistry and Molecular Biology
Bingjie Zhang, Shanmei Shen, Tianwei Gu, Ting Hong, Jiayi Liu, Jie Sun, Hongdong Wang, Yan Bi, Dalong Zhu
Polycystic ovary syndrome (PCOS) is a common metabolic disorder with hyperandrogenism as the core pathophysiologic feature. Increased bile acids and altered bile acid pool composition have been implicated in the pathogenesis of several metabolic diseases. Thus, this study aimed to clarify the specific alterations in circulating bile acids in patients with PCOS and investigate its associations with hyperandrogenism. We recruited 37 patients with PCOS and 35 age- and BMI-matched control subjects. Serum bile acids and androgen profiles were assessed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS)...
March 5, 2019: Journal of Steroid Biochemistry and Molecular Biology
Virginia Lope, María José Toribio, Beatriz Pérez-Gómez, Adela Castelló, Antonio Mena-Bravo, María Ángeles Sierra, Pilar Lucas, María Del Carmen Herrán-Vidaurrázaga, Carmen González-Vizcayno, Marina Nieves Pino, Inmaculada Cruz-Campos, Mª José Roca-Navarro, Nuria Aragonés, Isabelle Romieu, Mercedes Martínez-Cortés, María D Luque de Castro, Marina Pollán
The role of vitamin D in mammographic density is still unclear. This study examines the association between serum 25-hydroxyvitamin D (25(OH)D) and mammographic density, overall and by specific women characteristics. DDM-Madrid is a cross-sectional study that recruited 1403 premenopausal women in a breast radiodiagnosis unit of Madrid City Council. Information was collected with a questionnaire and plasma 25(OH)D was measured by solid-phase extraction on-line coupled to liquid chromatography-tandem mass spectrometry...
March 2, 2019: Journal of Steroid Biochemistry and Molecular Biology
Mohammed J Badran, Nicole Bertoletti, Aline Keils, Andreas Heine, Gerhard Klebe, Sandrine Marchais-Oberwinkler
17β-Hydroxysteroid dehydrogenase type 14 (17β-HSD14) catalyzes the conversion of highly active estrogens and androgens into their less active oxidized forms in presence of NAD+ as cofactor. The crystal structure of 17β-HSD14 has been determined, however, the role of individual amino acids likely involved in the enzymatic function remains poorly understood. Objective of this study was to further characterize the enzyme by site-directed mutagenesis considering five amino acids next to the catalytic center...
March 2, 2019: Journal of Steroid Biochemistry and Molecular Biology
Nada Zabaiou, Allan Fouache, Amalia Trousson, Julio Buñay-Noboa, Geoffroy Marceau, Vincent Sapin, Ahmed Zellagui, Silvère Baron, Mesbah Lahouel, Jean-Marc A Lobaccaro
Antiandrogens have a peculiar place in the treatment of metastatic prostate cancer by blocking the androgen receptor (AR). Unfortunately, aggressive tumors could rapidly develop into a castration resistant state. It is therefore essential to look for new molecules that are more effective, affecting not only the androgen signaling and with minimum undesirable effects. Natural products are an interesting source of new therapeutics, especially for cancer therapy as 70% of them have botanical origin. Based on an ethnobotany screening, we evaluated the effects of ethanolic extract of propolis (EEP) from Algeria on LNCaP cells...
March 1, 2019: Journal of Steroid Biochemistry and Molecular Biology
Flavia Fayet-Moore, Kaye E Brock, Jutta Wright, Leisa Ridges, Penelope Small, Markus J Seibel, Arthur D Conigrave, Rebecca S Mason
Low vitamin D status, measured as 25-hydroxyvitamin D (25OHD), has been linked to increased risk of osteoporosis and other disorders. Due to the indoor nature of office work, there may be an increased risk of 25OHD deficiency in this group. The aim of the current study was to evaluate seasonal variations of 25OHD in a population of healthy office workers, and to assess the effect of sun exposure behaviour, skin pigmentation, physical activity (PA) and dietary intake on serum 25OHD concentrations. We assessed the vitamin D status of healthy office workers in Sydney, Australia, at the end of summer (n = 103) and then at the end of winter (n = 71)...
March 1, 2019: Journal of Steroid Biochemistry and Molecular Biology
Maria Siekkeri Vandikas, Evelina Hellström, Per Malmberg, Amra Osmancevic
Recently it has been recognized that there is a need of investigating in detail the vitamin D synthesis and metabolism directly in the skin with respect to its possible autocrine and paracrine actions. The potential effects the active metabolite of vitamin D exerts in pathological skin conditions like psoriasis needs to be clarified. Under ultraviolet B (UVB) irradiation skin can autonomously synthesize, activate and degrade vitamin D. In this pilot case study, we used for the first time Time-of-flight secondary ion mass spectrometry (ToF-SIMS) in the analysis of skin biopsies from a patient with psoriasis before and after UVB phototherapy...
February 28, 2019: Journal of Steroid Biochemistry and Molecular Biology
Oliver Zierau, Annika Kolodziejczyk, Günter Vollmer, David Machalz, Gerhard Wolber, Detlef Thieme, Annekathrin Martina Keiler
Selective androgen receptor modulators comprise compounds that bind as ligands to the androgen receptor and possess tissue-selective activities. Ideally, they show agonistic properties in anabolic target tissues, while inducing antagonistic or only weak agonistic effects in reproductive organs. Due to their myoanabolic effects, selective androgen receptor modulators are included in the list of prohibited substances and methods of the World Anti-Doping Agency. In the current investigation, the androgenic potential of RAD-140, GSK-2881078 and GLPG0492 was comparably investigated in two different in vitro bioassays...
February 27, 2019: Journal of Steroid Biochemistry and Molecular Biology
Rachelle Gent, Therina du Toit, Liezl M Bloem, Amanda C Swart
The 11β-hydroxysteroid dehydrogenase (11βHSD) types 1 and 2 are primarily associated with glucocorticoid inactivation and reactivation. Several adrenal C11-oxy C19 and C11-oxy C21 steroids, which have been identified in prostate cancer, 21-hydroxylase deficiency and polycystic ovary syndrome, are substrates for these isozymes. This study describes the kinetic parameters of 11βHSD1 and 11βHSD2 towards the C11-keto and C11-hydroxy derivatives of the C19 and C21 steroids. The apparent Km and Vmax values indicate the more prominent 11βHSD2 activity towards 11β-hydroxy androstenedione, 11β-hydroxytestosterone and 11β-hydroxyprogesterone in contrast to the 11βHSD1 reduction of the C11-keto steroids, as was demonstrated in the LNCaP cell model in the production of 11-ketotestosterone and 11-ketodihydrotestosterone...
February 27, 2019: Journal of Steroid Biochemistry and Molecular Biology
Salndave B Skosana, John G Woodland, Meghan Cartwright, Kim Enfield, Maleshigo Komane, Renate Louw-du Toit, Zephne van der Spuy, Chanel Avenant, Donita Africander, Karl-Heinz Storbeck, Janet P Hapgood
Steroid hormones regulate a variety of physiological processes, including reproductive function, and are widely used in hormonal therapy. Synthetic progestogens, or progestins, were designed to mimic progesterone (P4 ) for use in contraception and hormonal replacement therapy in women. Medroxyprogesterone acetate (MPA) and norethisterone (NET) are the most widely used injectable contraceptives in the developing world, while other progestins such as levonorgestrel (LNG), etonogestrel (ETG) and nestorone (NES) are used in or being developed for other forms of contraception...
February 26, 2019: Journal of Steroid Biochemistry and Molecular Biology
Francesca Fortini, Francesco Vieceli Dalla Sega, Cristiana Caliceti, Elisabetta Lambertini, Antonio Pannuti, Daniel S Peiffer, Cristina Balla, Paola Rizzo
Estrogen regulates a plethora of biological processes, under physiological and pathological conditions, by affecting key pathways involved in the regulation of cell proliferation, fate, survival and metabolism. The Notch receptors are mediators of communication between adjacent cells and are key determinants of cell fate during development and in postnatal life. Crosstalk between estrogen and the Notch pathway intervenes in many processes underlying the development and maintenance of the cardiovascular system...
February 26, 2019: Journal of Steroid Biochemistry and Molecular Biology
Avinaash Maharaj, Ashwini Maudhoo, Li F Chan, Tatiana Novoselova, Rathi Prasad, Louise A Metherell, Leonardo Guasti
Hereditary adrenocorticotropin (ACTH) resistance syndromes encompass the genetically heterogeneous isolated or Familial Glucocorticoid Deficiency (FGD) and the distinct clinical entity known as Triple A syndrome. The molecular basis of adrenal resistance to ACTH includes defects in ligand binding, MC2R/MRAP receptor trafficking, cellular redox balance, cholesterol synthesis and sphingolipid metabolism. Biochemically, this manifests as ACTH excess in the setting of hypocortisolaemia. Triple A syndrome is an inherited condition involving a tetrad of adrenal insufficiency, achalasia, alacrima and neuropathy...
February 25, 2019: Journal of Steroid Biochemistry and Molecular Biology
Agnieszka Hryniewicka, Marta Malinowska, Tomasz Hauschild, Katarzyna Pieczul, Jacek W Morzycki
Imidazolium salts reveal interesting biological properties, especially regarding antitumor and antimicrobial activities. Two series of imidazolium salts based on steroids were obtained in an efficient and convenient synthesis. They were biologically tested to evaluate their antibacterial and antifungal properties. The activities of new salts, especially in relation to Gram-positive bacterial strains are comparable to the activities of known antibiotics. The most promising activity was that against C. albicans, which exceeded the antifungal activity of commonly used drugs...
February 20, 2019: Journal of Steroid Biochemistry and Molecular Biology
Andre Tchernof, Sheng Xiang Lin, Van Luu-The, Jacques Simard
No abstract text is available yet for this article.
February 16, 2019: Journal of Steroid Biochemistry and Molecular Biology
Stian Solheim, Samantha A Hutchinson, Elsa Lundanes, Steven R Wilson, James L Thorne, Hanne Roberg-Larsen
Oxysterols can contribute to proliferation of breast cancer through activation of the Estrogen Receptors, and to metastasis through activation of the Liver X Receptors. Endogenous levels of both esterified and free sidechain-hydroxylated oxysterols were examined in breast cancer tumours from Estrogen Receptor positive and negative breast tumours, using a novel fast liquid chromatography tandem mass spectrometry method. Multiple aliquots of five milligram samples of 22 tumours were analysed for oxysterol content to assess intra- and inter-tumour variation...
February 16, 2019: Journal of Steroid Biochemistry and Molecular Biology
Agnieszka Kotlarz, Małgorzata Przybyszewska, Paweł Swoboda, Jacek Neska, Joanna Miłoszewska, Monika Anna Grygorowicz, Andrzej Kutner, Sergiusz Markowicz
Conventional cytotoxic drugs preferentially eliminate differentiated cancer cells but spare relatively more resistant stem-like cancer cells capable to initiate recurrence. Due to cancer cell plasticity, the stem-like phenotype can be also acquired by cancer cells refractory to treatment with cytotoxic drugs. We investigated whether drugs inhibiting receptor tyrosine kinases could be used to target human colon cancer cells initiating cancer regrowth following conventional cytotoxic treatment. The moderately differentiated cell line HT-29 and poorly differentiated cell line HCT-116 were exposed to 5-fluorouracil (5-FU)...
February 14, 2019: Journal of Steroid Biochemistry and Molecular Biology
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