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Rachana Patel, Janis Fleming, Ernest Mui, Carolyn Loveridge, Peter Repiscak, Arnaud Blomme, Victoria Harle, Mark Salji, Imran Ahmad, Katy Teo, Freddie C Hamdy, Ann Hedley, Niels van den Broek, Gillian Mackay, Joanne Edwards, Owen J Sansom, Hing Y Leung
Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of treatment-resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre-clinical human and murine mCRPC models, we show that SPRY2 deficiency leads to an androgen self-sufficient form of CRPC Mechanistically, HER2-IL6 signalling axis enhances the expression of androgen biosynthetic enzyme HSD3B1 and increases SRB1-mediated cholesterol uptake in SPRY2-deficient tumours...
March 14, 2018: EMBO Molecular Medicine
Sara Falvo, Gabriella Chieffi Baccaria, Giuseppe Spaziano, Luigi Rosati, Massimo Venditti, Maria Maddalena Di Flore, Alessandra Santillo
The Harderian gland (HG) of the rat (Rattus norvegicus) secretes copious amounts of lipids, such as cholesterol. Here we report a study of the expressions of the StAR protein and key steroidogenic enzymes in the HG of male and female rats. The objective of the present investigation was to ascertain (a) whether the rat HG is involved in steroid production starting with cholesterol, and (b) whether the pattern of gene and protein expressions together with the enzymatic activities display sexual dimorphism. The results demonstrate, for the first time, the expression of StAR gene and protein, and Cyp11a1, Hsd3b1, Hsd17b3, Srd5a1, Srd5a2 and Cyp19a1 genes in the rat HG...
March 10, 2018: Comptes Rendus Biologies
Lanlan Chen, Yu Zhao, Linchao Li, Lubin Xie, Xianwu Chen, Jianpeng Liu, Xiaoheng Li, Lixu Jin, Xingwang Li, Ren-Shan Ge
Bisphenol A (BPA) is widely used in consumer products and a potential endocrine disruptor linked with sexual precocity. However, its action and underlying mechanisms on male sexual maturation is unclear. In the present study, we used a unique in vivo ethane dimethane sulfonate (EDS)-induced Leydig cell regeneration model that mimics the pubertal development of Leydig cells and an in vitro stem Leydig cell differentiation model to examine the roles of BPA in Leydig cell development in rats. Intratesticular exposure to doses (100 and 1000 pmol/testis) of BPA from post-EDS day 14-28 stimulated Leydig cell developmental regeneration process by increasing serum testosterone level and Leydig cell-specific gene (Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, and Hsd11b1) and their protein expression levels...
March 7, 2018: Molecular and Cellular Endocrinology
Tadayoshi Hayata, Masahiko Chiga, Yoichi Ezura, Makoto Asashima, Hidetaka Katabuchi, Ryuichi Nishinakamura, Masaki Noda
In mammals, the ovarian follicles are regulated at least in part by bone morphogenetic protein (BMP) family members. Dullard (also known as Ctdnep1) gene encodes a phosphatase that suppresses BMP signaling by inactivating or degrading BMP receptors. Here we report that the Col1a1-Cre-induced Dullard mutant mice displayed hemorrhagic ovarian cysts, with red blood cells accumulated in the follicles, resulting in infertility. Cells expressing Cre driven by Col1a1 2.3-kb promoter and their descendants were found in granulosa cells in the ovary and in Sertoli cells in the testis...
March 9, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
TaeSun Min, Ki-Ho Lee
Objective: Nandrolone decanoate (ND) is an anabolic-androgenic steroid frequently used for clinical treatment. However, the inappropriate use of ND results in the reduction of serum testosterone level and sperm production. The suppressive effect of ND on testosterone production has not been investigated in detail. The present study was designed to examine the effect of ND on the expression of steroidogenic enzymes in the rat testis. Methods: Male Sprague Dawley rats at 50 days of age were subcutaneously administrated with either 2 or 10 mg of ND/kg body weight/week for 2 or 12 weeks...
March 2, 2018: Asian-Australasian Journal of Animal Sciences
Meltem Weger, Nicolas Diotel, Benjamin D Weger, Tanja Beil, Andreas Zaucker, Helen L Eachus, James A Oakes, Jean Luc do Rego, Karl-Heinz Storbeck, Philipp Gut, Uwe Straehle, Sepand Rastegar, Ferenc Mueller, Nils Krone
The spatial and temporal expression of steroidogenic genes in zebrafish has not been fully characterized. Since zebrafish are increasingly employed in endocrine and stress research, a better characterization of steroidogenic pathways is required to target specific steps in the biosynthetic pathways in the future. Here, we have systematically defined the temporal and spatial expression of steroidogenic enzymes involved in glucocorticoid biosynthesis (cyp21a2, cyp11c1, cyp11a1, cyp11a2, cyp17a1, cyp17a2, hsd3b1, hsd3b2), as well as the mitochondrial electron-providing co-factors ferredoxin (fdx1, fdx1b) during zebrafish development...
February 27, 2018: Journal of Neuroendocrinology
Dragana Samardzija Nenadov, Kristina Pogrmic-Majkic, Svetlana Fa, Bojana Stanic, Aleksandra Tubic, Nebojsa Andric
Humans are exposed not only to single endocrine disruptors, but also to chemical mixtures that can adversely affect their reproductive health. Steroidogenesis in reproductive tissues is emerging as the key target of endocrine disruptor action. Here, we analyzed the effect of environmental chemical mixtures with estrogenic activity on steroidogenic processes in immature rat granulosa cells and whether the observed steroidogenic effects were mediated through estrogen receptors. Extracts from untreated wastewater were prepared by solid-phase extraction and silica gel fractionation...
February 13, 2018: Journal of Applied Toxicology: JAT
Kathrein von Kopylow, Wolfgang Schulze, Andrea Salzbrunn, Matthias Schaks, Elke Schäfer, Beate Roth, Stefan Schlatt, Andrej-Nikolai Spiess
STUDY QUESTION: Is it possible to induce in-vitro reorganization of primary human testis cells from testicular sperm extraction (TESE) biopsies, maintain their long-term cultivation in a 2D system and identify cellular compositions? SUMMARY ANSWER: In-vitro reorganization of primary human testis cells from TESE biopsies and their long-term cultivation on uncoated cell culture dishes is feasible and the cellular compositions can be uncovered through gene expression and microscopic analyses...
January 3, 2018: Molecular Human Reproduction
Daniel Hettel, Nima Sharifi
Patients with advanced prostate cancer who receive androgen deprivation therapy (ADT) almost invariably develop castration-resistant disease. The mechanism of resistance is largely based on synthesis of intratumoral androgens from adrenal precursors, requiring enzymatic action of 3β-hydroxysteroid dehydrogenase/Δ5→4 isomerase 1 (3β-HSD1), encoded by HSD3B1. A nucleotide polymorphism (1245A>C) in HSD3B1 results in a protein variant with increased steady-state levels and subsequently increased androgen synthesis from extragonadal precursors...
March 2018: Nature Reviews. Urology
Xiaojun Li, Jianpeng Liu, Siwen Wu, Wenwen Zheng, Huitao Li, Suhao Bao, Yong Chen, Xiaoling Guo, Lei Zhang, Ren-Shan Ge
Cadmium chloride (Cd) is a potent endocrine disruptor and may cause the malformation in the male reproductive tract. However, the effects of a single in utero exposure to low doses of Cd on fetal Leydig cell development are still unknown. The objective of this study is to investigate the effects of a single in utero exposure to low doses of Cd on rat fetal Leydig cell development. Adult 64-day-old Sprague-Dawley dams received a single intraperitoneal injection of 0, 0.25, 0.5, and 1.0 mg/kg Cd on gestational day 12...
March 2018: Chemosphere
Clemens Thoma
No abstract text is available yet for this article.
December 2017: Nature Reviews. Urology
Alisha Gupta, Jaswant Singh, Isabelle Dufort, Claude Robert, Fernanda Caminha Faustino Dias, Muhammad Anzar
Cryopreservation is known for its marked deleterious effects on embryonic health. Bovine compact morulae were vitrified or slow-frozen, and post-warm morulae were cultured to the expanded blastocyst stage. Blastocysts developed from vitrified and slow-frozen morulae were subjected to microarray analysis and compared with blastocysts developed from unfrozen control morulae for differential gene expression. Morula to blastocyst conversion rate was higher (P < 0.05) in control (72%) and vitrified (77%) than in slow-frozen (34%) morulae...
2017: PloS One
Xiaolong Wu, Jianpeng Liu, Yue Duan, Shiyu Gao, Yao Lü, Xiaoheng Li, Qiqi Zhu, Xianwu Chen, Jing Lin, Leping Ye, Ren-Shan Ge
Background: Tributyltin (TBT) is widely used as an antifouling agent that may cause reproductive toxicity. The mechanism of TBT on Leydig cell development is still unknown. The objective of the present study was to investigate whether a brief exposure to low doses of TBT permanently affects Leydig cell development and to clarify the underlying mechanism. Methods: Adult male Sprague Dawley rats were randomly assigned into four groups and gavaged normal saline (control), 0.1, 1.0, or 10.0 mg/kg/day TBT for a consecutive 10 days, respectively...
2017: Frontiers in Pharmacology
Jason W D Hearn, Wanling Xie, Mari Nakabayashi, Nima Almassi, Chad A Reichard, Mark Pomerantz, Philip W Kantoff, Nima Sharifi
Importance: The variant HSD3B1 (1245C) allele enhances dihydrotestosterone synthesis and predicts resistance to androgen-deprivation therapy (ADT) for biochemically recurrent prostate cancer after prostatectomy and for metastatic disease. Whether this is true after radiotherapy is unknown. Objective: To determine whether the HSD3B1 (1245C) allele predicts worse clinical outcomes from ADT for biochemical recurrence after radiotherapy. Design, Setting, and Participants: The Prostate Clinical Research Information System at Dana-Farber Cancer Institute was used to identify the study cohort, which included men treated with ADT for biochemical recurrence after primary radiotherapy between 1996 and 2013...
October 12, 2017: JAMA Oncology
Andrew W Hahn, Sumanta K Pal, Neeraj Agarwal
No abstract text is available yet for this article.
October 12, 2017: JAMA Oncology
Nima Almassi, Chad Reichard, Jianbo Li, Carly Russell, Jaselle Perry, Charles J Ryan, Terence Friedlander, Nima Sharifi
Importance: The HSD3B1 (1245C) germline variant encodes for a gain-of-function missense in 3β-hydroxysteroid dehydrogenase isoenzyme 1 (3βHSD1) that results in increased dihydrotestosterone synthesis from extragonadal precursors and is predictive of more rapid progression to castration-resistant prostate cancer (CRPC). Objective: To determine whether the HSD3B1 (1245C) genotype is predictive of clinical response to extragonadal androgen ablation with nonsteroidal 17α-hydroxylase/17,20-lyase (CYP17A1) inhibition in men with metastatic CRPC...
October 12, 2017: JAMA Oncology
Julio Buñay, Eduardo Larriba, Daniel Patiño-Garcia, Leonor Cruz-Fernandes, Sergio Castañeda-Zegarra, María Rodriguez-Fernandez, Jesús Del Mazo, Ricardo D Moreno
Endocrine-disrupting chemicals (EDCs) generate reproductive dysfunctions affecting the biosynthesis of steroid hormones and genes of the steroidogenic pathway. EDCs effects are mainly reported as a result of exposure to single compounds. However, humans are environmentally exposed to a mixture of EDCs. Herein, we assess chronic exposure to single alkylphenols and phthalates versus a mixture in mouse testes histology and steroidogenesis. Pregnant mice were exposed through drinking water to: 0.3 mg/Kg-body weight (BW)/day of each phthalate (DEHP, DBP, BBP), 0...
September 22, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
Xiaoling Guo, Songyi Zhou, Yong Chen, Xianwu Chen, Jianpeng Liu, Fei Ge, Qingquan Lian, Xiaomin Chen, Ren-Shan Ge
Ziram [zinc, bis (dimethyldithiocarbamate)] is an agricultural dithiocarbamate fungicide. By virtual screening, we have identified that ziram is a potential endocrine disruptor. To investigate its effects on pubertal development of Leydig cells, 35-day-old male Sprague Dawley rats orally received ziram (2 or 4 mg/kg/d) for 4 weeks and immature Leydig cells isolated from 35-day-old rat testes were treated with ziram (0.5-50 μM in vitro). Serum hormones, Leydig cell number and specific gene or protein expression levels after in vivo treatment were determined and medium androgen levels were measured as well as apoptosis of Leydig cells after in vitro treatment were determined...
December 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
Lanlan Chen, Xiaomin Chen, Xiaozhen Chen, Zhiyan Hu, Xiaoheng Li, Ying Su, Xingwang Li, Ren-Shan Ge
Placenta produces progesterone and estradiol for maintaining pregnancy. Two critical enzymes are responsible for their production: 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) that catalyzes the formation of progesterone from pregnenolone and aromatase that catalyzes the production of estradiol from testosterone. Fungicide ziram may disrupt the placental steroid production. In the present study, we investigated the effects of ziram on steroid formation in human placental cell line JEG-3 cells and on HSD3B1 and aromatase in the human placenta...
September 23, 2017: Steroids
Bayar K Zeebaree, Wing Y Kwong, George E Mann, Carlos G Gutierrez, Kevin D Sinclair
Our understanding of the effects of temperature on granulosa cell (GC) physiology is primarily limited to in vitro studies conducted under atmospheric (∼20% O2) conditions. In the current series of factorial experiments we identify important effects of O2 level (i.e. 5% vs 20% O2) on GC viability and steroidogenesis, and go onto report effects of standard (37.5 °C) vs high (40.0 °C) temperatures under more physiologically representative (i.e. 5%) O2 levels in the presence of different levels of melatonin (0, 20, 200 and 2000 pg/ml); a potent free-radical scavenger and abundant molecule within the ovarian follicle...
January 1, 2018: Theriogenology
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