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Journal of Steroid Biochemistry and Molecular Biology

Gustavo Monnerat, Fernando A C Seara, Joseph Albert Medeiros Evaristo, Gabriel Carneiro, Geisa Paulino Caprini Evaristo, Gilberto Domont, Jose Hamilton Matheus Nascimento, Jose Geraldo Mill, Fabio Cesar Souza Nogueira, Antonio Carlos Campos de Carvalho
Aging is a complex process that increases the risk of chronic disease development. Hormonal and metabolic alterations occur with aging, such as androgen activity decrease. Studies aim to understand the role of testosterone replacement therapy (TRT) in males, however biomarkers and the metabolic responses to TRT are not well characterized. Therefore, the present study investigated TRT effect in young adult and aged rats by metabolomics. Male Wistar rats were divided into four groups: adult and adult + testo (6months), old and old + testo (25-27months)...
June 16, 2018: Journal of Steroid Biochemistry and Molecular Biology
W Elger, B Schneider, Z Killeen, K Jewgenow, M Dehnhard, M Friedrich, B Santhamma, R Wedemeyer, K Nickisch
A guinea pig model for new HEC methods is proposed. Two targets for HEC (Hormonal Emergency Contraception), ovulation and conception (post-mating study), were investigated using adjusted PRM treatments: (a) Ovulation inhibition study: Injections on cycle days 10 - 17, study of ovarian histology on day 18; (b) post-mating study: Injections on cycle days 1 and 2; rate of pregnant females was recorded at autopsy on day 18. P plasma levels permitted assessment of effects on ovulation in non-conceiving animals. RESULTS: (a) All controls had recently ovulated...
June 11, 2018: Journal of Steroid Biochemistry and Molecular Biology
Manar A Elhinnawi, Rafat M Mohareb, Hanaa M Rady, Wagdy K B Khalil, Mervat M Abd Elhalim, Gamal A Elmegeed
A series of pregnenolone derivatives were synthesized and assessed for anti-cancer activity against hepatocellular carcinoma cell line (HepG2). The synthesized hetero-steroids (compounds 3, 4, 5, 6, 7, 8a and 8b) were evaluated for their cytotoxic activities using MTT (3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide) assay. Apoptotic activity was assessed using dual acridine orange/ethidium bromide staining method and DNA fragmentation assay. Pro-apoptotic genes (Bax and Bak) and anti-apoptotic genes (Bcl-2 and Bcl-xL) were analyzed using quantitative real time PCR...
June 10, 2018: Journal of Steroid Biochemistry and Molecular Biology
Carina Ankarberg-Lindgren, Jovanna Dahlgren, Mats X Andersson
BACKGROUND: Androgen and estrogen determinations serve as important diagnostic markers in a variety of clinical conditions. However, one challenge is to enhance assay sensitivity for determination in the lowest range, such as in prepubertal children. We here present a recently developed gas chromatography-tandem mass spectrometry (GC-MS/MS) method for determination of androstenedione (A4 ), dihydrotestosterone (DHT), testosterone (T), estrone (E1 ), and estradiol (E2 ) in children, which we have compared with the sensitive radioimmunoassays; E2 extraction-RIA and T-RIA...
June 9, 2018: Journal of Steroid Biochemistry and Molecular Biology
Maged Saleh, Christoph Welsch, Chengcong Cai, Claudia Döring, Jérôme Gouttenoire, Judith Friedrich, Katrin Haselow, Christoph Sarrazin, Klaus Badenhoop, Darius Moradpour, Stefan Zeuzem, Sabrina Rueschenbaum, Christian M Lange
BACKGROUND AND AIMS: Vitamin D signaling is involved in infectious and non-infectious liver diseases, yet the natural vitamin D metabolites are suboptimal therapeutic agents. In the present study, we therefore aimed to explore the potential and mechanism of selected calcitriol analogs to regulate the hepatocellular transcriptome and to inhibit hepatitis C virus (HCV) in comparison with calcitriol. METHODS: Human hepatoma cell lines and primary human macrophages were stimulated with calcitriol and selected calcitriol analogs...
June 7, 2018: Journal of Steroid Biochemistry and Molecular Biology
Vijay Boggula, Israel Hanukoglu, Ron Sagiv, Yehoshua Enuka, Aaron Hanukoglu
Pseudohypoaldosteronism type 1 (PHA) is a syndrome of unresponsiveness to aldosterone. The severe form of this disease results from mutations in the genes that encode for the epithelial sodium channel subunits, SCNN1A, SCNN1B, and SCNN1G. A PHA patient under our care failed to conceive after many years and IVF trials. Our earlier studies had shown that ENaC is expressed in the female reproductive tract. We hypothesized that a defective ENaC expression may be responsible for the infertility of the patient. To test this hypothesis we examined ENaC expression in endometrial Pipelle biopsy samples from three healthy women and the PHA patient with an Arg508X mutation in the SCNN1A gene...
June 6, 2018: Journal of Steroid Biochemistry and Molecular Biology
Yukiko Ogino, Saki Tohyama, Satomi Kohno, Kenji Toyota, Gen Yamada, Ryohei Yatsu, Tohru Kobayashi, Norihisa Tatarazako, Tomomi Sato, Hajime Matsubara, Anke Lange, Charles R Tyler, Yoshinao Katsu, Taisen Iguchi, Shinichi Miyagawa
No abstract text is available yet for this article.
June 6, 2018: Journal of Steroid Biochemistry and Molecular Biology
Matthew J Fuxjager, Eric R Schuppe
Sex steroids mediate the organization and activation of masculine reproductive phenotypes in diverse vertebrate taxa. However, the effects of sex steroid action in this context vary tremendously, in that steroid action influences reproductive physiology and behavior in markedly different ways (even among closely related species). This leads to the idea that the mechanisms underlying sex steroid action similarly differ across vertebrates in a manner that supports diversification of important sexual traits. Here, we highlight the Evolutionary Potential Hypothesis as a framework for understanding how androgen-dependent reproductive behavior evolves...
June 5, 2018: Journal of Steroid Biochemistry and Molecular Biology
Nasreen Choudhury, Sujit Kumar Sikdar
TWIK-related potassium channel 1 (TREK1), a two-pore domain potassium channel, is modulated by various hormones and neurotransmitters by activation of membrane receptor - coupled second messengers. 17β-estradiol is a neuromodulator capable of regulating several cellular processes including the activity of ion channels, in a rapid and non-genomic manner. The G protein-coupled estrogen receptor (GPER) is known to facilitate rapid actions of 17β-estradiol, though its role in modulation of ion channels is not widely explored...
June 5, 2018: Journal of Steroid Biochemistry and Molecular Biology
Michal Jurášek, Markéta Černohorská, Jiří Řehulka, Vojtěch Spiwok, Tetyana Sulimenko, Eduarda Dráberová, Maria Darmostuk, Soňa Gurská, Ivo Frydrych, Renata Buriánová, Tomáš Ruml, Marián Hajdúch, Petr Bartůněk, Pavel Dráber, Petr Džubák, Pavel B Drašar, David Sedlák
Microtubule dynamics is one of the major targets for new chemotherapeutic agents. This communication presents the synthesis and biological profiling of steroidal dimers based on estradiol, testosterone and pregnenolone bridged by 2,6-bis(azidomethyl)pyridine between D rings. The biological profiling revealed unique properties of the estradiol dimer including cytotoxic activities on a panel of 11 human cell lines, ability to arrest in the G2/M phase of the cell cycle accompanied with the attenuation of DNA/RNA synthesis...
May 24, 2018: Journal of Steroid Biochemistry and Molecular Biology
Xiaoye Sang, Hui Han, Donald Poirier, Sheng Xiang Lin
Steroid sulfatase is detectable in most hormone-dependent breast cancers. STX64, an STS inhibitor, induced tumor reduction in animal assay. Despite success in phase І clinical trial, the results of phase II trial were not that significant. Breast Cancer epithelial cells (MCF-7 and T47D) were treated with two STS inhibitors (STX64 and EM1913). Cell proliferation, cell cycle, and the concentrations of estradiol and 5α-dihydrotestosterone were measured to determine the endocrinological mechanism of sulfatase inhibition...
May 24, 2018: Journal of Steroid Biochemistry and Molecular Biology
Balázs Szili, Boglárka Szabó, Péter Horváth, Bence Bakos, Györgyi Kirschner, János P Kósa, Erzsébet Toldy, Zsuzsanna Putz, Péter Lakatos, Ádám Tabák, István Takács
Serum 25-hydroxyvitamin D /25OHD/ levels in humans are determined primarily by environmental factors such as UV-B radiation and diet, including vitamin D intake. Although some genetic determinants of 25OHD levels have been shown, the magnitude of this association has not yet been clarified. The present study evaluates the genetic contribution to total- /t-25OHD/ and free-25OHD /f-25OHD/ in a representative sample of the Hungarian population (n = 462). The study was performed at the end of winter to minimize the effect of sunlight, which is a major determinant of serum vitamin D levels...
May 21, 2018: Journal of Steroid Biochemistry and Molecular Biology
Cristina Amaral, Tiago Vieira Augusto, Elisiário Tavares-da-Silva, Fernanda M F Roleira, Georgina Correia-da-Silva, Natércia Teixeira
The leading cause of cancer death in women around the world is breast cancer. The aromatase inhibitors (AIs) are considered a first-line treatment for estrogen receptor-positive (ER+ ) breast tumors, in postmenopausal women. Exemestane (Exe) is a powerful steroidal AI, however, despite its therapeutic success, Exe-acquired resistance may occur leading to tumor relapse. Our group previously demonstrated that autophagy acts as a pro-survival process in Exe-induced cell death of ER+ sensitive breast cancer cells...
May 20, 2018: Journal of Steroid Biochemistry and Molecular Biology
Kai Huang, Li-Dong Wu
Dehydroepiandrosterone (DHEA), a 19-carbon steroid hormone primarily synthesized in the adrenal gland, exerts a chondroprotective effect against osteoarthritis (OA) and has been considered an effective candidate of disease-modifying OA drugs (DMOADs) that slow disease progression. We and others previously demonstrated that DHEA exerted a beneficial effect on osteoarthritic cartilage by positively modulating the balance between anabolic and catabolic factors (e.g., MMPs/TIMP-1, ADAMTS/TIMP-3 and cysteine proteinases/cystatin C), inhibiting catabolic signaling pathways (e...
May 19, 2018: Journal of Steroid Biochemistry and Molecular Biology
Alexander Slowik, Leoni Lammerding, Adib Zendedel, Pardes Habib, Cordian Beyer
Clinical and animal model studies have demonstrated the neuroprotective and anti-inflammatory effects of 17beta-estradiol (E2) and progesterone (P) in different disease models of the central nervous system (CNS) including ischemic stroke. Inflammasomes are involved in the interleukin-1 beta (IL1beta) maturation, in particular, NLRP3, the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and the active caspase-1 (Casp1) form. Recently, we showed that administration of E2 or P selectively regulated these components after experimental ischemic stroke in rats...
May 14, 2018: Journal of Steroid Biochemistry and Molecular Biology
Elina Nürnberg, Sandra Horschitz, Patrick Schloss, Andreas Meyer-Lindenberg
Glucocorticoids (GC) have first been shown to originate from the adrenal glands where synthesis and release is controlled by the hypothalamic-pituitary-adrenal (HPA) axis. Recently, it was shown that GC and other steroid hormones are also synthesized in the central nervous system, so-called neurosteroids. GC bind to specific GC receptors (GR) which function as ligand-activated transcription factors. GR are expressed in nearly all cell types in the brain, and therefore GC have a strong impact on neuronal development...
May 8, 2018: Journal of Steroid Biochemistry and Molecular Biology
Yonatan Amzaleg, Jie Ji, Donlaporn Kittivanichkul, Anna E Törnqvist, Sara Windahl, Elias Sabag, Aysha B Khalid, Hal Sternberg, Michael West, John A Katzenellenbogen, Susan A Krum, Nyam-Osor Chimge, Dustin E Schones, Yankel Gabet, Claes Ohlsson, Baruch Frenkel
Estrogens attenuate bone turnover by inhibiting both osteoclasts and osteoblasts, in part through antagonizing Runx2. Apparently conflicting, stimulatory effects in osteoblast lineage cells, however, sway the balance between bone resorption and bone formation in favor of the latter. Consistent with this dualism, 17ß-estradiol (E2) both stimulates and inhibits Runx2 in a locus-specific manner, and here we provide evidence for such locus-specific regulation of Runx2 by E2 in vivo. We also demonstrate dual, negative and positive, regulation of Runx2-driven alkaline phosphatase (ALP) activity by increasing E2 concentrations in ST2 osteoblast progenitor cells...
May 8, 2018: Journal of Steroid Biochemistry and Molecular Biology
Maliha T Munir, Christopher Ponce, Catherine A Powell, Kaiser Tarafdar, Teru Yanagita, Mahua Choudhury, Lauren S Gollahon, Shaikh M Rahman
Breast cancer is one of the most commonly diagnosed cancers in women. Accumulating evidence suggests that cholesterol plays an important role in the development of breast cancer. Even though the mechanistic link between these two factors is not well understood, one possibility is that dysregulated cholesterol metabolism may affect lipid raft and membrane fluidity and can promote tumor development. Current studies have shown oxysterol 27-hydroxycholesterol (27-HC) as a critical regulator of cholesterol and breast cancer pathogenesis...
May 4, 2018: Journal of Steroid Biochemistry and Molecular Biology
Christian Solís-Calero, Taize M Augusto, Hernandes F Carvalho
The androgen receptor (AR) promoter contains guanine-rich regions that are able to fold into polymorphic G-quadruplex (GQ) structures, and whose deletion decreases AR gene transcription. Our attention was focused on this region because of the frequent termination of sequencing reactions during promoter methylation studies. UV and circular dichroism (CD) spectroscopy of synthetic oligonucleotides encompassing these guanine-rich regions suggested a parallel quadruplex topology with three guanine quartets and three side loops in the three cases...
April 28, 2018: Journal of Steroid Biochemistry and Molecular Biology
Anita Kumar, Kushaan Dumasia, Sharvari Deshpande, Sanketa Raut, N H Balasinor
Estrogen receptors (ERα and β) and androgen receptor (AR) regulate various critical processes during spermatogenesis. Since spermatogenesis is very sensitive to hormonal stimuli and perturbations, it is important to understand the regulation of expression of these receptors by sex steroid hormones. Although many studies have reported deregulation of steroid receptors on endocrine disruption, there is no consensus on the regulation of their expression by steroid hormones during spermatogenesis, and a lack of clear understanding of the mechanism of regulation...
April 27, 2018: Journal of Steroid Biochemistry and Molecular Biology
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