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K G Sorwell, L Renner, A R Weiss, M Neuringer, S G Kohama, H F Urbanski
Estradiol supplementation has been shown to enhance cognitive performance in old ovariectomized rhesus macaques (Macaca mulatta). To determine if similar benefits could be achieved in perimenopausal animals using alternative hormonal supplements we administered dehydroepiandrosterone (DHEA) to old ovary-intact female rhesus macaques for ~2.5 months. Using computerized touchscreen memory tasks, including delayed response (DR) and delayed matching-to-sample (DMS), we observed improved performance with time in all of the animals but failed to detect a significant effect of DHEA...
October 13, 2016: Genes, Brain, and Behavior
Stefan Z Lutz, Andreas Peter, Fausto Machicao, Apostolia Lamprinou, Jürgen Machann, Fritz Schick, Ingmar Königsrainer, Alfred Königsrainer, Andreas Fritsche, Harald Staiger, Hans-Ulrich Häring, Norbert Stefan, Konstantinos Kantartzis
CONTEXT/OBJECTIVE: Acute pharmacological inhibition of 11β-hydroxysteroid-dehydrogenase 1 (11β-HSD1), which converts cortisone into the much more potent cortisol in peripheral tissues, results in reduction of total-, visceral- and liver fat, but not of insulin resistance. We now investigated whether lifelong alterations of 11β-HSD1 activity similarly affect these cardiometabolic risk parameters, by studying single nucleotide polymorphisms (SNPs) in the 11β-HSD1-coding gene (HSD11B1)...
October 7, 2016: Journal of Clinical Endocrinology and Metabolism
Charlotte Sefton, Erika Harno, Alison Davies, Helen Small, Tiffany-Jayne Allen, Jonathan R Wray, Catherine B Lawrence, Anthony P Coll, Anne White
Glucocorticoid (Gc) excess, from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognised to cause adverse metabolic side effects. The Gc receptor (GR) is widely expressed throughout the body, including brain regions such as the hypothalamus. However the extent to which chronic Gcs affect Gc concentrations in the hypothalamus and impact on GR and target genes is unknown. To investigate this, we used a murine model of corticosterone-induced obesity, and analysed corticosterone levels in the hypothalamus and expression of genes relevant to Gc action...
September 20, 2016: Endocrinology
Jean Z Lin, Stephen R Farmer
In this issue of Genes & Development, Zeng and colleagues (pp. 1822-1836) identify lysine-specific demethylase 1 (LSD1) as a pivotal regulator of whole-body energy expenditure by controlling the oxidative and thermogenic activity of brown adipose tissue (BAT). They show that LSD1 interacts with PRDM16 to repress select white adipose tissue (WAT) genes but also represses hydroxysteroid 11-β-dehydrogenase 1 (HSD11B1) independently of PRDM16 to prevent production of glucocorticoids that impair BAT functions. Their study provides important insight into epigenetic mechanisms regulating the function of BAT...
August 15, 2016: Genes & Development
Xing Zeng, Mark P Jedrychowski, Yi Chen, Sara Serag, Gareth G Lavery, Steve P Gygi, Bruce M Spiegelman
Brown adipocytes display phenotypic plasticity, as they can switch between the active states of fatty acid oxidation and energy dissipation versus a more dormant state. Cold exposure or β-adrenergic stimulation favors the active thermogenic state, whereas sympathetic denervation or glucocorticoid administration promotes more lipid accumulation. Our understanding of the molecular mechanisms underlying these switches is incomplete. Here we found that LSD1 (lysine-specific demethylase 1), a histone demethylase, regulates brown adipocyte metabolism in two ways...
August 15, 2016: Genes & Development
Xiaomin Chen, Yaoyao Dong, Shuyan Cao, Xiaoheng Li, Zhe Wang, Ruijie Chen, Ren-Shan Ge
Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants. PBDEs have been widely used in textiles, flexible polyurethane foams, electronic components, electrical components, and plastics. 11β-Hydroxysteroid dehydrogenases, isoform 1 (HSD11B1) and isoform 2 (HSD11B2), have been demonstrated to be the regulators of local glucocorticoid levels. In this study, the potencies of 4 different PBDEs (BDE-3, BDE-47, BDE-100, and BDE-153) with 1-6 bromine atoms attached in inhibition of rat and human HSD11B1 and HSD11B2 activities were compared to 4-bromobiphenyl (BBP), a structurally similar compound...
2016: Pharmacology
Saori Itoi-Ochi, Mika Terao, Hiroyuki Murota, Ichiro Katayama
Keratinocytes are known to synthesize cortisol through activation of the enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). To confirm the function of 11β-HSD1 in keratinocytes during inflammation in vivo, we created keratinocyte-specific-11β-HSD1 knockout mice (K5-Hsd11b1-KO mice) and analyzed the response to narrow-band ultraviolet B (NB-UVB) irradiation. Firstly, we measured the mRNA and protein levels of 11β-HSD1 following NB-UVB irradiation and found that the expression of 11β-HSD1 in keratinocytes of mouse ear skin was enhanced at 3 and 24 hours after 250 mJ/cm(2), 500 mJ/cm(2), 1 J/cm(2), and 2 J/cm(2) NB-UVB irradiation...
January 2016: Dermato-endocrinology
Erwin Lemche, Oleg S Chaban, Alexandra V Lemche
Impact of environmental stress upon pathophysiology of the metabolic syndrome (MetS) has been substantiated by epidemiological, psychophysiological, and endocrinological studies. This review discusses recent advances in the understanding of causative roles of nutritional factors, sympathomedullo-adrenal (SMA) and hypothalamic-pituitary adrenocortical (HPA) axes, and adipose tissue chronic low-grade inflammation processes in MetS. Disturbances in the neuroendocrine systems for leptin, melanocortin, and neuropeptide Y (NPY)/agouti-related protein systems have been found resulting directly in MetS-like conditions...
2016: Frontiers in Neuroscience
Charlotte Hellgren, Åsa Edvinsson, Jocelien D Olivier, Romina Fornes, Elisabet Stener-Victorin, S J Kumari A Ubhayasekera, Alkistis Skalkidou, Jonas Bergquist, Inger Sundström-Poromaa
Maternal serum cortisol has been suggested to be influenced by psychiatric morbidity, and may also influence fetal growth. However, several studies found equal cortisol levels in depressed and healthy pregnant women. Placental 11-β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) shields the fetus from maternal cortisol by conversion to cortisone, a function that may be compromised by maternal stress. We aimed to compare the serum ratio of cortisone to cortisol, in women with and without psychiatric morbidity during pregnancy...
July 2016: Psychoneuroendocrinology
Marta Fichna, Magdalena Żurawek, Maria Gryczyńska, Anna Sowińska, Jerzy Nowak, Marek Ruchała
No abstract text is available yet for this article.
June 2016: European Journal of Internal Medicine
Mika Terao, Saori Itoi, Sayaka Matsumura, Lingli Yang, Hiroyuki Murota, Ichiro Katayama
Over the past decade, extra-adrenal cortisol production was reported in various tissues. The enzyme that catalyzes the conversion of hormonally inactive cortisone into active cortisol in cells is 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). We recently reported that 11β-HSD1 is also expressed in keratinocytes and regulates inflammation and keratinocyte proliferation. To investigate the function of 11β-HSD1 in keratinocytes during inflammation in vivo, we created keratinocyte-specific 11β-HSD1 knockout (K5-Hsd11b1-KO) mice and analyzed the inflammatory response in models of hapten-induced contact irritant dermatitis...
June 2016: American Journal of Pathology
Xiaoheng Li, Baiping Mao, Yaoyao Dong, Yuan Li, Meizheng Zhan, Yanfang Bai, Qingquan Lian, Ren-Shan Ge, Leping Ye
Ziram is a widely used fungicide for crops. Its endocrine disrupting action is largely unknown. 11β-Hydroxysteroid dehydrogenases, isoforms 1 (HSD11B1) and 2 (HSD11B2), have been demonstrated to be the regulators of the local levels of active glucocorticoids, which have broad physiological actions. In the present study, the potency of ziram was tested for its inhibition of rat and human HSD11B1 and HSD11B2. Ziram showed the inhibition of rat HSD11B1 reductase with IC50 of 87.07 μM but no inhibition of human enzyme at 100 μM...
March 21, 2016: Chemical Research in Toxicology
Andrea M Allan, Alexander K Hafez, Matthew T Labrecque, Elizabeth R Solomon, M Nabil Shaikh, Xianyun Zheng, Abdulmehdi Ali
Previously we have shown that prenatal moderate arsenic exposure (50 ppb) disrupts glucocorticoid receptor (GR) programming and that these changes continue into adolescence in males. However, it was not clear what the molecular mechanisms were promoting these GR programming changes or if these changes occurred in arsenic-exposed females. In the present studies, we assessed the effects of arsenic on protein and mRNA of the glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase (Hsd) isozymes and compared the levels of methylation within the promoters of the Nr3c1 and Hsd11b1 genes in female fetal brain at embryonic days (E) 14 and 18...
October 2015: Toxicology Reports
Michael K Wong, Alison C Holloway, Daniel B Hardy
Nicotine exposure during pregnancy leads to placental insufficiency impairing both fetal and neonatal development. Previous studies from our laboratory have demonstrated that in rats, nicotine augmented endoplasmic reticulum (ER) stress in association with placental insufficiency; however, the underlying mechanisms remain elusive. Therefore, we sought to investigate the possible direct effect of nicotine on ER stress in Rcho-1 rat placental trophoblast giant (TG) cells during differentiation. Protein and/or mRNA expression of markers involved in ER stress (eg, phosphorylated PERK, eIF2α, CHOP, and BiP/GRP78) and TG cell differentiation and function (eg, Pl-1, placental growth factor [Pgf], Hsd11b1, and Hsd11b2) were quantified via Western blot or real-time polymerase chain reaction...
May 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Ágnes Molnár, Annamária Kövesdi, Nikolette Szücs, Miklós Tóth, Péter Igaz, Károly Rácz, Attila Patócs
OBJECTIVE: Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined. CONTEXT: To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease...
August 2016: Clinical Endocrinology
Yuan Lu, Nicholas Starkey, Wei Lei, Jilong Li, Jianlin Cheng, William R Folk, Dennis B Lubahn
Sutherlandia frutescens (L) R. Br. (Sutherlandia) is a South African botanical that is traditionally used to treat a variety of health conditions, infections and diseases, including cancer. We hypothesized Sutherlandia might act through Gli/ Hedgehog (Hh)-signaling in prostate cancer cells and used RNA-Seq transcription profiling to profile gene expression in TRAMPC2 murine prostate cancer cells with or without Sutherlandia extracts. We found 50% of Hh-responsive genes can be repressed by Sutherlandia ethanol extract, including the canonical Hh-responsive genes Gli1 and Ptch1 as well as newly distinguished Hh-responsive genes Hsd11b1 and Penk...
2015: PloS One
Yuan Lu, Jilong Li, Jianlin Cheng, Dennis B Lubahn
BACKGROUND: Nuclear receptor family member, Estrogen related receptor β, and the Hedgehog signal transduction pathway are both reported to relate to tumorigenesis and induced pluripotent stem cell reprogramming. We hypothesize that Estrogen related receptor β can modulate the Hedgehog signaling pathway and affect Hedgehog driven downstream gene expression. RESULTS: We established an estrogen related receptor β-expressing Hedgehog-responsive NIH3T3 cell line by Esrrb transfection, and performed mRNA profiling using RNA-Seq after Hedgehog ligand conditioned medium treatment...
2015: BMC Molecular Biology
Linxi Li, Ying Wu, Xiaolong Wu, Huang Wang, Yanfang Bai, Xiudi Wang, Benson T Akingbemi, Ping Huang, Ren-Shan Ge
Butylated hydroxyanisole (BHA) is a widely used antioxidant for food preservation. 11β-hydroxysteroid dehydrogenases, isoforms 1 (HSD11B1) and 2 (HSD11B2) have been demonstrated to be the regulators of the local level of active glucocorticoid, which has a broad range of physiological actions. In this study, the potency of BHA was tested for the inhibition of HSD11B1 and HSD11B2 in rat and human tissues. BHA showed potent inhibition of HSD11B2 with the half maximal inhibitory concentration calculated at 13...
2016: Pharmacology
Xingwang Li, Guoxin Hu, Xiaoheng Li, Yi-Yan Wang, Yuan-Yuan Hu, Hongyu Zhou, Syed A Latif, David J Morris, Yanhui Chu, Zhiqiang Zheng, Ren-Shan Ge
BACKGROUND: 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) interconverts active 11β-hydroxyl glucocorticoids and inactive 11keto forms. However, its directionality is determined by availability of NADP+/NADPH. In liver cells, 11β-HSD1 behaves as a primary reductase, while in Leydig cells it acts as a primary oxidase. However, the exact mechanism is not clear. The direction of 11β-HSD1 has been proposed to be regulated by hexose-6-phosphate dehydrogenase (H6PDH), which catalyzes glucose-6-phosphate (G6P) to generate NADPH that drives 11β-HSD1 towards reduction...
2015: PloS One
Masafumi Tetsuka, Ryo Takagi, Nobuhiro Ambo, Thet Su Myat, Yuta Zempo, Asuka Onuma
Glucocorticoid action in target organs is regulated by relative activities of 11β-HSD type 1 (HSD11B1) that mainly converts cortisone to active cortisol and type 2 (HSD11B2) that inactivates cortisol to cortisone. HSD11Bs have been shown to be expressed in the ovary of various species. However, little is known about the expression and activity of HSD11Bs in the bovine cumulus-oocyte complex (COC). In the present study, we investigated the expression and activities of HSD11Bs in in vitro-matured (IVM) bovine COCs...
January 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
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