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Journal of Steroid Biochemistry and Molecular Biology

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https://www.readbyqxmd.com/read/28442393/progesterone-receptors-pr-mediate-stat-actions-pr-and-prolactin-receptor-signaling-crosstalk-in-breast-cancer-models
#1
Katherine A Leehy, Thu H Truong, Laura J Mauro, Carol A Lange
Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in contrast, is the primary driver of mammary epithelial cell proliferation in adulthood. The high circulating levels of progesterone during pregnancy signal through PR, inducing expression of the prolactin receptor (PRLR). Cooperation between PR and prolactin (PRL) signaling, via regulation of downstream components in the PRL signaling pathway including JAKs and STATs, facilitates the alveolar morphogenesis observed during pregnancy...
April 22, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28442392/4-chlorodiazepam-is-neuroprotective-against-amyloid-beta-in-organotypic-hippocampal-cultures
#2
B D Arbo, J B Hoppe, K Rodrigues, L M Garcia-Segura, C G Salbego, M F Ribeiro
The translocator protein (TSPO) is an outer mitochondrial membrane protein involved in the transport of cholesterol into the mitochondria, which is the first step for the synthesis of steroid hormones, as well as in the regulation of mitochondrial permeability transition pore opening and apoptosis. Studies have shown that the activation of TSPO may promote neuroprotective actions in experimental models of neurodegeneration and brain injury. In a previous study, our group showed that 4'-chlorodiazepam (4'-CD), a TSPO ligand, was neuroprotective against amyloid-beta (Aβ) in SHSY-5Y neuroblastoma cells...
April 22, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28428023/cyp450s-analysis-across-spiny-lobster-metamorphosis-identifies-a-long-sought-missing-link-in-crustacean-development
#3
Tomer Ventura, Utpal Bose, Quinn P Fitzgibbon, Gregory G Smith, P Nicholas Shaw, Scott F Cummins, Abigail Elizur
Cytochrome P450s (CYP450s) are a rapidly evolving family of enzymes, making it difficult to identify bona fide orthologs with notable lineage-specific exceptions. In ecdysozoans, a small number of the most conserved orthologs include enzymes which metabolize ecdysteroids. Ecdysone pathway components were recently shown in a decapod crustacean but with a notable absence of shade, which is important for converting ecdysone to its active form, 20-hydroxyecdysone (20HE), suggesting that another CYP450 performs a similar function in crustaceans...
April 17, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28428022/cloning-and-identification-of-a-novel-steroid-11%C3%AE-hydroxylase-gene-from-absidia-coerulea
#4
Ruijie Wang, Pengcheng Sui, Xiangjiang Hou, Tong Cao, Longgang Jia, Fuping Lu, Suren Singh, Zhengxiang Wang, Xiaoguang Liu
Steroid 11-hydroxylation by filamentous fungi is a major route for industrial scale production of key intermediates in the synthesis of steroid drugs. Although it is well established that enzymes involved in fungal hydroxylation of steroids are cytochrome P450s (CYP), few fungal steroid hydroxylase genes have been identified. In this study, we identified a novel 11α-hydroxylase gene CYP5311B1 from Absidia coerulea AS3.65 by a combination of transcriptome sequencing, Real-Time qRT-PCR and heterologous expression in Pichia pastoris...
April 17, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28412323/single-cpg-site-methylation-controls-estrogen-receptor-gene-transcription-and-correlates-with-hormone-therapy-resistance
#5
Kouki Tsuboi, Takamasa Nagatomo, Tatsuyuki Gohno, Toru Higuchi, Shunta Sasaki, Natsu Fujiki, Masafumi Kurosumi, Hiroyuki Takei, Yuri Yamaguchi, Toshifumi Niwa, Shin-Ichi Hayashi
Hormone therapy is the most effective treatment for patients with estrogen receptor α-positive breast cancers. However, although resistance occurs during treatment in some cases and often reflects changed estrogen receptor α status, the relationship between changes in estrogen receptor α expression and resistance to therapy are poorly understood. In this study, we identified a mechanism for altered estrogen receptor α expression during disease progression and acquired hormone therapy resistance in aromatase inhibitor-resistant breast cancer cell lines...
April 12, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28411181/monoclonal-antibodies-to-the-reactive-centre-loop-rcl-of-human-corticosteroid-binding-globulin-cbg-can-protect-against-proteolytic-cleavage
#6
John G Lewis, Peter A Elder
Corticosteroid-binding globulin (CBG) binds most of the cortisol in circulation and is a non-functional member of the family of serine protease inhibitors (serpins) with an exposed elastase sensitive reactive centre loop (RCL). The RCL can be cleaved by human neutrophil elastase, released from activated neutrophils, and can also be cleaved at nearby site(s) by elastase released by Pseudomonas aeruginosa, and at two further sites, also within the RCL, by bovine chymotrypsin. Cleavage of the RCL results in a conformational change accompanied by a marked decrease in affinity for cortisol and hence its release at the site of proteolysis...
April 12, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28408351/inhibition-of-heat-shock-protein-90-rescues-glucocorticoid-induced-bone-loss-through-enhancing-bone-formation
#7
Haixiao Chen, Ji Xing, Xinhua Hu, Lihua Chen, Haiyan Lv, Chengyun Xu, Dun Hong, Ximei Wu
Endogenous glucocorticoids (GCs) support normal bone development and bone mass maintenance, whereas long-term exposure to pharmacological dosages of GCs uncouples bone formation and resorption, resulting in GC-induced osteoporosis (GIOP). Heat shock protein 90 (HSP90) chaperoning glucocorticoid receptor (GR) signaling prompts us to speculate that HSP90 plays critical roles in GC-mediated bone formation and GIOP. In the present study, inhibition of HSP90 activity by 17-Demethoxy-17-allyaminogeldanmycin (17-AAG) or knockdown of HSP90 expression by siRNAs attenuated dexamethasone(Dex)-induced GR nuclear accumulation and transcriptional output of GR signaling, whereas overexpression of HSP90α or HSP90β enhanced GR transactivity in C3H10T1/2 cells...
April 10, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28408350/neuroactive-steroid-levels-and-psychiatric-and-andrological-features-in-post-finasteride-patients
#8
Roberto Cosimo Melcangi, Daniele Santi, Roberto Spezzano, Maria Grimoldi, Tommaso Tabacchi, Maria Letizia Fusco, Silvia Diviccaro, Silvia Giatti, Giuseppe Carrà, Donatella Caruso, Manuela Simoni, Guido Cavaletti
Recent reports show that, in patients treated with finasteride for male pattern hair loss, persistent side effects including sexual side effects, depression, anxiety and cognitive complaints may occur. We here explored the psychiatric and andrological features of patients affected by post-finasteride syndrome (PFS) and verified whether the cerebrospinal fluid (CSF) and plasma levels of neuroactive steroids (i.e., important regulators of nervous function) are modified. We found that eight out of sixteen PFS male patients considered suffered from a DSM-IV major depressive disorder (MDD)...
April 10, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28396197/anti-tumor-efficacy-of-new-7%C3%AE-substituted-androstanes-as-aromatase-inhibitors-in-hormone-sensitive-and-resistant-breast-cancer-cells
#9
Cristina Amaral, Carla L Varela, João Maurício, Ana Filipa Sobral, Saul C Costa, Fernanda M F Roleira, Elisiário J Tavares-da-Silva, Georgina Correia-da-Silva, Natércia Teixeira
The majority of breast cancer cases are estrogen receptor positive (ER(+)). Although, third-generation aromatase inhibitors (AIs) are used as first-line treatment in post-menopausal women, they cause endocrine resistance and bone loss, which limits their success. Therefore, there is a demand to discover new potent molecules, with less toxicity that can circumvent these drawbacks. Our group has previously demonstrated that new 7α-substituted steroidal molecules, 7α-(2ξ,3ξ-epoxypropyl)androsta-1,4-diene-3,17-dione (3), 7α-allylandrost-4-ene-3,17-dione (6), 7α-allylandrost-4-en-17-one (9), 7α-allyl-3-oxoandrosta-1,4-dien-17β-ol (10) and 7α-allylandrosta-1,4-diene-3,17-dione (12) are potent AIs in placental microsomes...
April 7, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28377308/cell-type-specific-regulatory-effects-of-glucocorticoids-on-cutaneous-tlr2-expression-and-signalling
#10
Qi Su, Anja Pfalzgraff, Günther Weindl
Glucocorticoids (GCs) induce Toll-like receptor (TLR) 2 expression and synergistically upregulate TLR2 with pro-inflammatory cytokines or bacteria. These paradoxical effects have drawn attention to the inflammatory initiating or promoting effects of GCs, as GC treatment can provoke inflammatory skin diseases. Here, we aimed to investigate the regulatory effects of GCs in human skin cells of different epidermal and dermal layers. We found that Dex induced TLR2 expression mainly in undifferentiated and less in calcium-induced differentiated keratinocytes but not in HaCaT cells or fibroblasts, however, Dex reduced TLR1/6 expression...
April 1, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28373106/umbilical-cord-blood-androgen-levels-in-girls-and-boys-assessed-by-gas-chromatography-tandem-mass-spectrometry
#11
Anna-Carin Lundell, Henrik Ryberg, Liesbeth Vandenput, Anna Rudin, Claes Ohlsson, Åsa Tivesten
Androgen exposure of the fetus during gestation plays an important role in human physiology and pathophysiology, but assessment of androgens, in particular dihydrotestosterone (DHT), in human umbilical cord blood is technically challenging. The aim of this study was to assess umbilical cord androgen levels, including DHT, at birth by a highly sensitive assay, and study their association with sex of the infant, sex-hormone-binding globulin (SHBG) levels, and gestational age at delivery. Swedish infants (27 girls, 26 boys) were recruited at maternity care clinics in Southern Sweden...
March 31, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28347854/twenty-years-of-the-g-protein-coupled-estrogen-receptor-gper-historical-and-personal-perspectives
#12
Matthias Barton, Edward J Filardo, Stephen J Lolait, Peter Thomas, Marcello Maggiolini, Eric R Prossnitz
Estrogens play a critical role in many aspects of female physiology, particularly reproductive function, but also in pathophysiology, and are associated with protection from numerous diseases in premenopausal women. Steroids and particularly estrogen action have been known for ∼90 years, with the first evidence for a receptor for estrogen presented ∼50 years ago. The original ancestral steroid receptor, extending back into evolution more than 500 million years, was likely an estrogen receptor, whereas G protein-coupled receptors (GPCRs) trace their origins back into history more than one billion years...
March 25, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28343901/gper-blockers-as-nox-downregulators-a-new-drug-class-to-target-chronic-non-communicable-diseases
#13
Matthias R Meyer, Matthias Barton
Oxidative stress is a hallmark of chronic non-communicable diseases such as arterial hypertension, diabetes, coronary artery disease, and stroke. Cardiovascular diseases are characterized by increased production of reactive oxygen species (ROS) by NAPDH oxidase 1 (Nox1) and additional Nox isoforms among other sources. Activation of the G protein-coupled estrogen receptor (GPER) can mediate multiple salutary effects on the cardiovascular system. However, GPER also has constitutive activity, e.g. in the absence of specific agonists, that was recently shown to promote hypertension and aging-induced tissue damage by enabling Nox1-derived production of ROS...
March 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28342973/effects-of-a-sustained-release-formulation-of-1-25-dihydroxyvitamin-d3-glycosides-for-milk-fever-prevention-on-serum-1-25-dihydroxyvitamin-d3-calcium-and-phosphorus-in-dairy-cows
#14
Heinrich Bachmann, Michael Lanz, Susanne Kehrle, Wolfgang Bittner, Annick Toggenburger, Georg A Mathis, Walter Rambeck
Milk fever (MF) is a metabolic disease in dairy cows around parturition. The clinical lead sign is muscular paresis leading in severe cases to paralysis of the affected animal. Multiparturient animals of high performing dairy breeds are most likely to be affected and have a high probability of recurrence. An acute drop in blood calcium levels causes the disease when the demand for calcium at the onset of lactation exceeds the ability to replete blood calcium levels through mobilization from bone and intestinal uptake...
March 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28341251/vitamin-d-and-muscle-function
#15
Bess Dawson-Hughes
Muscle weakness is a hallmark of severe vitamin D deficiency, but the effect of milder vitamin D deficiency or insufficiency on muscle mass and performance and risk of falling is uncertain. In this presentation, I review the evidence that vitamin D influences muscle mass and performance, balance, and risk of falling in older adults. Special consideration is given to the impact of both the starting 25-hydroxyvitamin D [25(OH)D] level and the dose administered on the clinical response to supplemental vitamin D in older men and women...
March 21, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28330721/changes-in-the-human-transcriptome-upon-vitamin-d-supplementation
#16
Yvonne Pasing, Christopher Graham Fenton, Rolf Jorde, Ruth Hracky Paulssen
Vitamin D is hydroxylated in the liver and kidneys to its active form, which can bind to the vitamin D receptor (VDR). The VDR is present in a wide variety of different cells types and tissues and acts as a transcription factor. Although activation of the VDR is estimated to regulate expression of up to 5% of the human genome, our study is the first analysing gene expression after supplementation in more than 10 subjects. Subjects of a randomized controlled trial (RCT) received either vitamin D3 (n47) in a weekly dose of 20,000 IU or placebo (n 47) for a period of three to five years...
March 19, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28330720/attenuation-of-uvr-induced-vitamin-d3-synthesis-in-a-mouse-model-deleted-for-keratinocyte-lathosterol-5-desaturase
#17
Anastasia M Makarova, Saloni Pasta, Gordon Watson, Cedric Shackleton, Ervin H Epstein
The lower risk of some internal cancers at lower latitudes has been linked to greater sun exposure and consequent higher levels of ultraviolet radiation (UVR)-produced vitamin D3 (D3). To separate the experimental effects of sunlight and of all forms of D3, a mouse in which UVR does not produce D3 would be useful. To this end we have generated mice carrying a modified allele of sterol C5-desaturase (Sc5d), the gene encoding the enzyme that converts lathosterol to 7-dehydrocholesterol (7-DHC), such that Sc5d expression can be inactivated using the Cre/lox site-specific recombination system...
March 19, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28323044/medium-doses-of-vitamin-d-decrease-falls-and-higher-doses-of-daily-vitamin-d3-increase-falls-a-randomized-clinical-trial
#18
Lynette M Smith, Gallagher J Christopher, Suiter Corinna
Falls are a serious health problem in the aging population. Because low levels of vitamin D have been associated with increased fall rates, many trials have been performed with vitamin D; two meta-analyses showed either a small effect or no effect of vitamin D on falls. We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D (25OHD) and data on falls was collected as a secondary outcome. In a 12-month double blind randomized placebo trial, elderly women, mean age 66 years, were randomized to one of seven daily oral doses of vitamin D or placebo...
March 17, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28323043/high-dose-vitamin-d-may-improve-lower-urinary-tract-symptoms-in-postmenopausal-women
#19
Johanna Oberg, Margareta Verelst, Rolf Jorde, Kevin Cashman, Guri Grimnes
Lower urinary tract symptoms (LUTS) are common in postmenopausal women, and have been reported inversely associated with vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D levels. The aim of this study was to investigate if high dose vitamin D supplementation would affect LUTS in comparison to standard dose. In a randomized controlled study including 297 postmenopausal women with low bone mineral density, the participants were allocated to receive capsules of 20 000 IU of vitamin D3 twice a week (high dose group) or similar looking placebo (standard dose group)...
March 17, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28323042/comparison-of-intravaginal-0-5-prasterone-0-3mg-conjugated-estrogens-and-10%C3%AE-g-estradiol-on-estrogen-related-symptoms-of-vulvovaginal-atrophy
#20
REVIEW
David F Archer, Fernand Labrie, Marlene Montesino, Céline Martel
The objective is to compare the effect of intravaginal dehydroepiandrosterone (DHEA, prasterone), conjugated equine estrogens (CEE) and estradiol (E2) on moderate to severe dyspareunia and/or vaginal dryness. In a review of available data, independent prospective, randomized, double-blind and placebo-controlled Phase III 12-week clinical trials involved daily administration of 6.5mg (0.50%) prasterone, daily (21days on/7days off) 0.3mg CEE, twice weekly 0.3mg CEE or 10 μg E2 daily for 2 weeks followed by twice weekly for 10 weeks...
March 17, 2017: Journal of Steroid Biochemistry and Molecular Biology
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