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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
Akira Matsumoto, Hiroyuki Murota, Mika Terao, Ichiro Katayama
Intense chronic itch significantly reduces quality of life for atopic dermatitis (AD) patients, impairing daily activity. While abnormal itch sensation can be induced by innocuous stimuli, known as alloknesis, the mechanisms driving this process remain obscure. Psychological and environmental stimuli are known to aggravate AD symptoms. Recently, the enzyme 11β-hydroxysteroid dehydrogenase-1 (HSD11β1), which is expressed in keratinocytes, has been implicated in maintaining homeostasis against environmental stimuli by activating endogenous glucocorticoids (GCs)...
February 20, 2018: Journal of Investigative Dermatology
Sofia Christakoudi, Manohursingh Runglall, Paula Mobillo, Irene Rebollo-Mesa, Tjir-Li Tsui, Estefania Nova-Lamperti, Sonia Norris, Yogesh Kamra, Rachel Hilton
Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-qPCR-based) and cell counts were adjusted for immunosuppressant drug intake. Tolerant (n = 17), stable (n = 190) and CR patients (n = 37) were compared...
February 7, 2018: Molecular and Cellular Endocrinology
Qiqi Zhu, Fei Ge, Yaoyao Dong, Wei Sun, Zhe Wang, Yuanyuan Shan, Ruijie Chen, Jianliang Sun, Ren-Shan Ge
Many flavonoids and isoflavonoids have anti-diabetic effects in animal models. However, the mechanisms that are involved are generally unclear. Since 11β-hydroxysteroid dehydrogenases (HSD11Bs) play important roles in diabetes, we hypothesize that flavonoids and isoflavonoids may affect diabetes by targeting two isoforms of HSD11B differently. The inhibitory effects of flavonoids (apigenin and quercetin) and isoflavonoids [genistein and (±) equol] on rat and human HSD11B1 and HSD11B2 were analyzed. The potencies of inhibition on human HSD11B1 reductase was in the order of apigenin > quercetin > genistein > (±) equol, with IC50 values of 2...
February 6, 2018: Steroids
Wei Zhang, Li Qian, Maya Deyssenroth, Luca Lambertini, Jackie Finik, Jacob Ham, Yongling Huang, Kenji J Tsuchiya, Patricia Pehme, Jessica Buthmann, Sachiko Yoshida, Jia Chen, Yoko Nomura
Prenatal maternal stress increases the risk for negative developmental outcomes in offspring, however the underlying biological mechanisms remain largely unexplored. In this study, alterations in placental gene expression associated with maternal stress were examined to elucidate potential underlying epi/genetic mechanisms. Expression levels of 40 selected genes involved in regulating fetal HPA-axis and neurodevelopment were profiled in placental tissues collected from a birth cohort established around the time of Superstorm Sandy...
February 9, 2018: Journal of Neuroendocrinology
X Zou, P Ramachandran, T J Kendall, A Pellicoro, E Dora, R L Aucott, K Manwani, T Y Man, K E Chapman, N C Henderson, S J Forbes, S P Webster, J P Iredale, B R Walker, Z Michailidou
A hallmark of chronic liver injury is fibrosis, with accumulation of extracellular matrix orchestrated by activated hepatic stellate cells (HSCs). Glucocorticoids (GC) limit HSC activation in vitro and tissue GC levels are amplified by 11beta-hydroxysteroid dehydrogenase-1 (11βHSD1). Although 11βHSD1 inhibitors have been developed for type 2 diabetes mellitus and improve diet-induced fatty liver in various mouse models, effects on the progression and/or resolution of liver injury and consequent fibrosis have not been characterised...
December 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
D F Cobice, D E W Livingstone, A McBride, C L MacKay, B R Walker, S P Webster, R Andrew
11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1; EC generates active glucocorticoid hormones. Small molecule inhibitors have been developed to target 11β-HSD1 for the treatment of dementia; these must enter brain subregions, such as the hippocampus, to be effective. We previously reported mass spectrometry imaging measurement of murine tissue steroids, and deuterated steroid tracer infusion quantification of 11 β -HSD1 turnover in humans. Here, these tools are combined to assess tissue pharmacokinetics and pharmacodynamics of an 11 β -HSD1 inhibitor that accesses the brain...
December 14, 2017: Biochemical Pharmacology
Hee Young Kang, Young-Kwon Choi, Yeon Ik Jeong, Kyung-Chul Choi, Sang-Hwan Hyun, Woo-Suk Hwang, Eui-Bae Jeung
Cortisol is a steroid hormone essential to the maintenance of homeostasis that is released in response to stress and low blood glucose concentration. Cortisol is converted from cortisone by 11βhydroxysteroid dehydrogenase type 1 (HSD11B1). It has been reported that too much cortisol or overexpression of HSD11B1 induces obesity and the insulin resistance that accompanies metabolic syndrome in rodent adipose tissue. In our previous study, HSD11B1 -transgenic (TG) fibroblasts were established, and a porcine model was generated by SCNT using those fibroblasts...
December 5, 2017: International Journal of Molecular Sciences
Manu Verma, Tiina M J Kipari, Zhenguang Zhang, Tak Yung Man, Thorsten Forster, Natalie Z M Homer, Jonathan R Seckl, Megan C Holmes, Karen E Chapman
Chronically elevated glucocorticoid levels impair cognition and are pro-inflammatory in the brain. Deficiency or inhibition of 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1), which converts inactive into active glucocorticoids, protects against glucocorticoid-associated chronic stress- or age-related cognitive impairment. Here, we hypothesised that 11β-HSD1 deficiency attenuates the brain cytokine response to inflammation. Because inflammation is associated with altered energy metabolism, we also examined the effects of 11β-HSD1 deficiency upon hippocampal energy metabolism...
November 21, 2017: Brain, Behavior, and Immunity
Nani Wang, Guizhi Zhao, Yang Zhang, Xuping Wang, Lisha Zhao, Pingcui Xu, Dan Shou
BACKGROUND Osteoporosis is a complex bone disorder with a genetic predisposition, and is a cause of health problems worldwide. In China, Curculigo orchioides (CO) has been widely used as a herbal medicine in the prevention and treatment of osteoporosis. However, research on the mechanism of action of CO is still lacking. The aim of this study was to identify the absorbable components, potential targets, and associated treatment pathways of CO using a network pharmacology approach. MATERIAL AND METHODS We explored the chemical components of CO and used the five main principles of drug absorption to identify absorbable components...
October 27, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Mototsugu Fukaya
BACKGROUND: The skin produces cortisol by itself and regulates its own proliferation and differentiation. There is a possibility that topical corticosteroids (TCSs) influence the cortisol homeostasis in the skin. AIMS AND OBJECTIVES: The author described the density and distribution of cortisol and its parties in the epidermis after application of topical steroids immunohistologically. MATERIALS AND METHODS: The forearm skin was biopsied before and after 2 weeks' application of clobetasol propionate 0...
July 2017: Indian Journal of Dermatology
Xin-Rui Qi, Sabina Luchetti, Ronald W H Verwer, Arja A Sluiter, Matthew R J Mason, Jiang-Ning Zhou, Dick F Swaab
Altered levels of steroids have been reported in the brain, cerebral spinal fluid and plasma of patients with mood disorders. Neuroimaging studies have reported both functional and structural alterations in mood disorders, for instance in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC). In order to determine whether the endogenous production of steroids is altered in the ACC and DLPFC of patients with major depressive disorder (MDD) or bipolar disorder (BPD), quantitative real-time PCR was performed to detect mRNA expression level of key enzymes in the steroid biosynthetic pathways...
July 27, 2017: Brain Pathology
Nayana Devang, Kapaettu Satyamoorthy, Padmalatha S Rai, M Nandini, Satish Rao, Nagaraja M Phani, Prabha Adhikari
BACKGROUND: 11beta-hydroxysteroid dehydrogenase Type 1 (11β-HSD1) is an NADP or NADPH-dependent enzyme that generates cortisol from cortisone for a local glucocorticoid action. Functional polymorphisms within 11beta-hydroxysteroid dehydrogenase Type 1 (HSD11B1) gene have shown an association with various factors, including insulin resistance (IR) and hypertension. In our study, we have assessed the association of HSD11B1 (rs12086634 and rs846910) gene polymorphisms with type 2 diabetes (T2D) and metabolic syndrome (metS)...
July 13, 2017: Diabetes Research and Clinical Practice
Agnieszka E Zielinska, Rachel S Fletcher, Mark Sherlock, Craig L Doig, Gareth G Lavery
Glucocorticoids are important for skeletal muscle energy metabolism, regulating glucose utilization, insulin sensitivity, and muscle mass. Nicotinamide adenine dinucleotide phosphate-dependent 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)-mediated glucocorticoid activation in the sarcoplasmic reticulum (SR) is integral to mediating the detrimental effects of glucocorticoid excess in muscle. 11β-Hydroxysteroid dehydrogenase type 1 activity requires glucose-6-phosphate transporter (G6PT)-mediated G6P transport into the SR for its metabolism by hexose-6-phosphate dehydrogenase (H6PDH) for NADPH generation...
July 2017: Cell Biochemistry and Function
Xiaolong Wu, Xiaoling Guo, Huang Wang, Songyi Zhou, Lili Li, Xiaomin Chen, Guimin Wang, Jianpeng Liu, Hong-Shan Ge, Ren-Shan Ge
Cadmium is an endocrine disruptor, impairing male reproduction. The objective of this study is to investigate whether cadmium affects rat Leydig cell regeneration and to dissect the underlying mechanism. Adult male Sprague-Dawley rats received a single intraperitoneal injection (i.p.) of 0, 0.5 or 1.0 mg/kg of cadmium chloride, followed by ethane dimethane sulfonate (EDS) treatment to eliminate adult Leydig cells 20 days later. Compared to control (0 dose), cadmium treatment reduced serum testosterone levels by days 21, 35, and 56 after EDS treatment...
July 24, 2017: Scientific Reports
Lourdes Rocamora-Reverte, Holger M Reichardt, Andreas Villunger, GJan Wiegers
Glucocorticoids (GC) are essential regulators of T-cell development and function. Activation of the immune system increases systemic adrenal-derived GC levels which downregulate immune activity as part of a negative feedback control system. Increasing evidence shows, however, that GC can also be derived from extra-adrenal sources such as the thymus or intestine, thus providing local control of GC-mediated effects. The thymus reportedly produces GC, but whether thymic epithelial cells or thymocytes produce GC acting either in an autocrine or paracrine fashion is not clear...
July 20, 2017: Cell Death & Disease
Zhenguang Zhang, Agnes E Coutinho, Tak Yung Man, Tiina M J Kipari, Patrick W F Hadoke, Donald M Salter, Jonathan R Seckl, Karen E Chapman
11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) predominantly converts inert glucocorticoids into active forms, thereby contributing to intracellular glucocorticoid levels. 11β-HSD1 is dynamically regulated during inflammation, including in macrophages where it regulates phagocytic capacity. The resolution of inflammation in some disease models including inflammatory arthritis is impaired by 11β-HSD1 deficiency or inhibition. However, 11β-HSD1 deficiency/inhibition also promotes angiogenesis, which is beneficial in mouse models of surgical wound healing, myocardial infarction or obesity...
September 2017: Journal of Endocrinology
Veera Vihma, Jussi Naukkarinen, Ursula Turpeinen, Esa Hämäläinen, Jaakko Kaprio, Aila Rissanen, Sini Heinonen, Antti Hakkarainen, Jesper Lundbom, Nina Lundbom, Tomi S Mikkola, Matti J Tikkanen, Kirsi H Pietiläinen
Obesity and ageing are associated with lower serum testosterone levels in men. How fat distribution or adipose tissue metabolism, independent of genetic factors and age, are related to sex steroid metabolism is less clear. We studied the associations between adiposity and serum sex hormone concentrations, and mRNA expression of genes regulating sex hormone metabolism in adipose tissue in young adult male monozygotic (MZ) twin pairs. The subjects [n=18 pairs; mean age, 32 years; individual body mass indexes (BMIs) 22-36kg/m2 ] included 9 male MZ twin pairs discordant for BMI [intra-pair difference (Δ) in BMI ≥3kg/m2 ]...
September 2017: Journal of Steroid Biochemistry and Molecular Biology
Sung Noh Hong, Je-Gun Joung, Joon Seol Bae, Chan Soo Lee, Ja Seol Koo, Soo Jung Park, Jong Pil Im, You Sun Kim, Ji Won Kim, Woong Yang Park, Young-Ho Kim
BACKGROUND: Aberrant gene expression in the gut mucosa might contribute to the initiation and progression of Crohn's disease (CD). RNA sequencing (RNA-seq) provides precise measurements of expression levels of transcripts and their isoforms. The aim of this study was to use RNA-seq to investigate transcriptomic differences and identify significantly differentially expressed transcripts in inflamed and noninflamed intestinal mucosa of CD patients. METHODS: RNA-seq was performed on 13 pairs of inflamed and noninflamed intestinal mucosa from 13 CD patients and on sex-matched normal mucosa of 13 healthy controls...
July 2017: Inflammatory Bowel Diseases
Anju Elizabeth Thomas, Padmavathi J N Inagadapa, Sugeetha Jeyapal, Naga Muralidhar Merugu, Rajender Rao Kalashikam, Raghunath Manchala
Magnesium plays a major role in many vital functions in the body. We reported earlier that maternal magnesium restriction altered body composition, fat metabolism, and insulin resistance in WNIN rat offspring and was associated with increased glucocorticoid stress in the offspring in their later life. We hypothesize that increased glucocorticoid stress and inflammation which originate in Mg restricted rat dams is transmitted through placenta to the fetus and underlie the metabolic disturbances in the later life of the offspring...
May 27, 2017: Biological Trace Element Research
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