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Endocrinology

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https://www.readbyqxmd.com/read/28666321/androgens-regulate-ovarian-gene-expression-through-modulation-of-ezh2-expression-and-activity
#1
Xiaoting Ma, Emily Hayes, Anindita Biswas, Christina Seger, Hen Prizant, Stephen R Hammes, Aritro Sen
Significant evidence suggests that androgen signaling through classical androgen receptors is critical for both normal and pathologic ovarian physiology. Specifically, we and others have shown that, in mouse granulosa cells, androgen actions through both extra-nuclear and nuclear androgen receptor signaling are critical for normal follicle development and ovulation. Here we show that androgens through the PI3K/Akt pathway rapidly (within minutes) phosphorylate and inhibit activity of the Polycomb group protein enhancer of zeste homologue 2 (Ezh2)...
June 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/28658938/low-thyroid-hormone-levels-disrupt-thyrotrope-development
#2
Ksenia Tonyushkina, Stefanie Krug, Theresa Ortiz-Toro, Tibor Mascari, Rolf Karlstrom
Low thyroid hormone (TH) conditions caused by a variety of pre- and perinatal problems have been shown to alter postnatal regulatory thyrotropin (TSH) responsiveness to TH in humans and rodents. The mechanisms underlying this pituitary TH-resistance remain unknown. Here we use the evolutionarily conserved zebrafish model to examine the effects of low TH on thyrotrope development and function. Zebrafish were exposed to the goitrogen 6-propyl-2-thiouracil (PTU) in order to block TH synthesis and this led to an approximately 50% increase in thyrotrope numbers and a 8-10 fold increase in tshb mRNA abundance in 2 week old larvae and 1 month old juveniles...
June 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28651331/il-1%C3%AE-up-regulates-star-and-progesterone-production-through-the-erk1-2-and-p38-mediated-creb-signaling-pathways-in-human-granulosa-lutein-cells
#3
Xuan Dang, Qinling Zhu, Yaqiong He, Yuan Wang, Yao Lu, Xiaoxue Li, Jia Qi, Hasiximuke Wu, Yun Sun
The pro-inflammatory cytokine interleukin-1β (IL-1β) may be involved in several ovulation-associated events, such as proteases synthesis, prostaglandin production and steroidogenesis in granulosa cells. However, the exact effect of IL-1β on progesterone synthesis in granulosa cells and the underlying mechanism remain unclear. By using cultured granulosa-lutein cells collected from women undergoing in vitro fertilization or intracytoplasmic sperm injection, we found that IL-1β up-regulated steroidogenic acute regulatory protein (StAR) expression and progesterone synthesis in granulosa-lutein cells, which was comparable with luteinizing hormone (LH) effect and could be abolished by an IL-1 receptor antagonist...
June 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28651330/rosiglitazone-improves-insulin-resistance-mediated-by-10-12-conjugated-linoleic-acid-in-a-male-mouse-model-of-metabolic-syndrome
#4
Shari Wang, Leela Goodspeed, Katherine E Turk, Barbara Houston, Laura J den Hartigh
Trans-10, cis-12 conjugated linoleic acid (10,12 CLA) is a dietary fatty acid that promotes weight loss and disproportionate fat loss. Obese mice fed a high fat high sucrose (HFHS) diet containing 10,12 CLA are resistant to weight gain and contain markedly reduced subcutaneous fat and adiponectin, with a concurrent lack of improvement in insulin sensitivity despite significant weight loss. Taken together, 10,12 CLA promotes a phenotype resembling PPARγ antagonism. Since thiazolidinediones such as rosiglitazone (Rosi) are used clinically to improve insulin sensitivity by activating PPARγ, with particular efficacy in subcutaneous white adipose tissue, we hypothesized that Rosi would improve glucose metabolism in mice losing weight with 10,12 CLA...
June 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28645209/genome-wide-mapping-of-in-vivo-er%C3%AE-binding-sites-in-male-mouse-efferent-ductules
#5
Guangxin Yao, Shuanggang Hu, Lu Yu, Yanfei Ru, Charlie Degui Chen, Qiang Liu, Yonglian Zhang
As an important nuclear hormone receptor, estrogen receptor alpha (ERα), which is encoded by Esr1 gene, regulates the expression of hundreds of genes in a stimulus-specific, temporal and tissue-specific fashion, mainly by binding to specific DNA sequences-estrogen response elements (EREs). As an important estrogen target tissue in males, the function of the efferent ductules relies on the presence of the ERα protein, but the underlying regulatory mechanisms are poorly illustrated. In this study, genome-wide ERα-binding sites in mouse efferent ductules were mapped by ChIP-seq...
June 22, 2017: Endocrinology
https://www.readbyqxmd.com/read/28645193/irf6-regulates-alternative-activation-by-suppressing-ppar%C3%AE-in-male-murine-macrophages
#6
Chuan Li, Wei Ying, Zheping Huang, Tyler Brehm, Andrew Morin, Anthony T Vella, Beiyan Zhou
Aberrant pro-inflammatory and suppressed anti-inflammatory (alternative) macrophage activation underlies the chronic inflammation associated with obesity and other metabolic disorders. This study demonstrates a novel role for Interferon Regulatory Factor 6 (IRF6) in regulating macrophage alternative activation (M2) by suppressing peroxisome proliferator-activated receptor-γ (PPARγ) expression, a critical regulator of alternative macrophage polarization. The data demonstrate suppression of IRF6 in both M2 macrophages and obese adipose tissue macrophages (ATMs)...
June 22, 2017: Endocrinology
https://www.readbyqxmd.com/read/28637206/improving-combination-osteoporosis-therapy-in-a-preclinical-model-of-heightened-osteoanabolism
#7
Yu Shao, Selene Hernandez-Buquer, Paul Childress, Keith R Stayrook, Marta B Alvarez, Hannah Davis, Lilian Plotkin, Yongzheng He, Keith W Condon, David B Burr, Stuart J Warden, Alexander G Robling, Feng-Chun Yang, Ronald C Wek, Matthew R Allen, Joseph P Bidwell
Combining anti-catabolic agents with parathyroid hormone (PTH) to enhance bone mass has yielded mixed results in osteoporosis patients. Towards the goal of enhancing the efficacy of these regimens, we tested their utility in combination with loss of the transcription factor Nmp4 since disabling this gene amplifies PTH-induced increases in trabecular bone in mice by boosting osteoblast secretory activity. We addressed whether combining a sustained anabolic response with an anti-catabolic results in superior bone acquisition compared to PTH mono-therapy...
June 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/28633442/continuous-glucose-monitoring-in-female-nod-mice-reveals-daily-rhythms-and-a-negative-correlation-with-body-temperature
#8
Ron Korstanje, Jennifer L Ryan, Holly S Savage, Bonnie L Lyons, Kevin G Kane, Stacey J Sukoff Rizzo
Previous studies with continuous glucose monitoring in mice have been limited to several days or weeks, with the mouse's physical attachment to the equipment impacting behavior and measurements. In the current study we measured blood glucose and body temperature at 10-second intervals for 12 weeks in a cohort of NOD/ShiLtJ female mice using wireless telemetry. This allowed us, for the first time, to obtain a high-resolution profile of the circadian rhythm of these two parameters and the onset of hyperglycemic development in real time...
June 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28633436/membrane-androgen-receptor-zip9-induces-croaker-ovarian-cell-apoptosis-via-stimulatory-g-protein-alpha-subunit-and-mapkinase-signaling
#9
Aubrey Converse, Chenan Zhang, Peter Thomas
Recent studies show that androgen-induced apoptosis in Atlantic croaker primary granulosa/theca (G/T) cells and in human breast and prostate cancer cell lines is mediated by the novel membrane androgen receptor ZIP9 which belongs to the SLC39A zinc transporter family. However, the apoptotic signaling pathways remain unclear because ZIP9 activates an inhibitory G protein in human cancer cells, whereas recombinant croaker ZIP9 activates a stimulatory G protein (Gs) in transfected cancer cells. Here we investigated androgen-dependent apoptotic pathways in order to identify the signaling pathways regulated through wild-type croaker ZIP9 in ovarian follicle cells...
June 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28637315/attenuated-effects-of-bile-acids-on-glucose-metabolism-and-insulin-sensitivity-in-a-male-mouse-model-of-prenatal-undernutrition
#10
Huijuan Ma, Vicencia M Sales, Ashley R Wolf, Sathish Subramanian, Tucker J Matthews, Michael Chen, Aparna Sharma, Walt Gall, Wim Kulik, David E Cohen, Yusuke Adachi, Nicholas W Griffin, Jeffrey I Gordon, Mary-Elizabeth Patti, Elvira Isganaitis
Prenatal undernutrition and low birth weight are associated with risk of type 2 diabetes and obesity. Prenatal caloric restriction results in low birth weight, glucose intolerance, obesity, and reduced plasma bile acids (BA) in offspring mice. Since BAs can regulate systemic metabolism and glucose homeostasis, we hypothesized that BA supplementation could prevent diet-induced obesity and glucose intolerance in this model of developmental programming. Pregnant dams were food restricted by 50% from gestational days 12...
June 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28637283/an-essential-physiological-role-for-mct8-in-bone-in-male-mice
#11
Victoria D Leitch, Caterina Di Cosmo, Xiao-Hui Liao, Sam O'Boy, Thomas M Galliford, Holly Evans, Peter I Croucher, Alan Boyde, Alexandra Dumitrescu, Roy E Weiss, Samuel Refetoff, Graham R Williams, J H Duncan Bassett
T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter-8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compound mutants, which additionally lack the ability to convert the prohormone T4 to the active hormone T3...
June 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28605466/lhcgr-expression-during-fsh-induced-follicle-growth-is-negatively-regulated-by-eukaryotic-initiation-factor-5a
#12
Thippeswamy Gulappa, Bindu Menon, K M J Menon
We have shown that the transient changes in the expression of LHCGR mRNA during the ovarian cycle occurs, at least in part, through a post-transcriptional mechanism involving an LHCGR mRNA binding protein (LRBP). Eukaryotic initiation factor 5A (eIF5A), an LRBP-interacting protein, participates in this process. EIF5A undergoes hypusination, a unique post-translational modification, which is necessary for its functions. The present study examined the role of eIF5A in FSH-induced LHCGR expression during follicular growth...
June 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28591806/quantitative-proteomics-of-intestinal-mucosa-from-male-mice-lacking-intestinal-epithelial-insulin-receptors
#13
Stina Rikke Jensen, Erwin M Schoof, Sarah E Wheeler, Henning Hvid, Jonas Ahnfelt-Rønne, Bo Falck Hansen, Erica Nishimura, Grith Skytte Olsen, Thomas Kislinger, Patricia L Brubaker
The goal of the present study was to determine whether loss of the insulin receptor alters the molecular landscape of the intestinal mucosa, using intestinal-epithelial insulin receptor knockout (IE-irKO) mice and both genetic (IRfl/fl and Villin-cre) controls. Quantitative proteomic analysis by Liquid Chromatography Mass Spectrometry (LC-MS) was applied to jejunal and colonic mucosa from mice fed a chow- or Western diet (WD). Jejunal mucosa from IE-irKO mice demonstrated alterations in all intestinal cell linages, Paneth, goblet, absorptive and enteroendocrine cells, whereas only goblet and absorptive cells were affected in the colon...
June 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/28591779/elucidating-the-biological-roles-of-insulin-and-its-receptor-in-murine-intestinal-growth-and-function
#14
Stina Rikke Jensen, Sarah E Wheeler, Henning Hvid, Jonas Ahnfelt-Rønne, Bo Falck Hansen, Erica Nishimura, Grith Skytte Olsen, Patricia L Brubaker
The role of the intestinal insulin receptor (IR) is not well-understood. We therefore explored the effect of insulin (300 nmol/kg-d for 12d) on the intestine in sex-matched C57Bl/6J mice. The intestinal and metabolic profiles were also characterized in male and female intestinal-epithelial IR knockout (IE-irKO) mice as compared to all genetic controls, on a chow or Western diet (WD) for 4-12wk. Insulin treatment did not affect intestinal size, intestinal resistance or metabolic genes, but reduced proximal-colon crypt depth and acutely increased colonic AKT activation...
June 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/28591769/functional-characterisation-of-xenopus-thyroid-hormone-transporters-mct8-and-oatp1c1
#15
Bilal B Mughal, Michelle Leemans, Elaine C L de Souza, Sébastien le Mevel, Petra Spirhanzlova, Theo Visser, Jean-Baptiste Fini, Barbara A Demeneix
Xenopus is an excellent model for studying thyroid hormone signalling as it undergoes thyroid hormone-dependent metamorphosis. Despite the fact that receptors and deiodinases have been described in Xenopus, membrane transporters for these hormones are yet to be characterised. We cloned Xenopus monocarboxylate transporter 8 (mct8) and organic anion transporting polypeptide 1C1 (oatpc1c1), focusing on these two transporters given their importance for vertebrate brain development. Protein alignment and bootstrap analysis showed that Xenopus mct8 and oatp1c1 are closer to their mammalian orthologues than their teleost counterparts...
June 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/28586439/ramp2-influences-glucagon-receptor-pharmacology-via-trafficking-and-signaling
#16
Jaimini Cegla, Ben J Jones, James V Gardiner, David J Hodson, Thomas Marjot, Emma R McGlone, Tricia M Tan, Stephen R Bloom
Endogenous satiety hormones provide an attractive target for obesity drugs. Glucagon causes weight loss by reducing food intake and increasing energy expenditure. To further understand the cellular mechanisms by which glucagon and related ligands activate the glucagon receptor (GCGR), we have investigated the interaction of the GCGR with RAMP2, a member of the family of Receptor Activity Modifying Proteins.We have used a combination of competition binding experiments, cell surface ELISA, functional assays assessing the Gαs and Gq pathways and β-arrestin recruitment, and siRNA knockdown to examine the effect of RAMP2 on the GCGR...
June 6, 2017: Endocrinology
https://www.readbyqxmd.com/read/28586424/role-of-er%C3%AE-in-mediating-female-uterine-transcriptional-responses-to-igf1
#17
Sylvia C Hewitt, Wipawee Winuthayanon, Sydney L Lierz, Katherine J Hamilton, Lauren J Donoghue, J Tyler Ramsey, Sara A Grimm, Yukitomo Arao, Kenneth S Korach
Estrogen (E2) signaling through its nuclear receptor, estrogen receptor α (ERα) increases insulin-like growth factor 1 (IGF1) in the rodent uterus, which then initiates further signals via the IGF1 receptor (IGF1R). Directly administering IGF1 results in similar biological and transcriptional uterine responses. Our studies using global ERα-null mice demonstrated a loss of uterine biological responses of the uterus to E2 or IGF1 treatment, while maintaining transcriptional responses to IGF1. To address this discrepancy in the need for uterine ERα in mediating the IGF1 transcriptional vs...
June 6, 2017: Endocrinology
https://www.readbyqxmd.com/read/28586412/high-fat-diet-and-female-fertility
#18
Natalie M Hohos, Malgorzata E Skaznik-Wikiel
The prevalence of obesity is high among reproductive age women and is associated with impaired reproductive function. Obesity is multifactorial in origin, yet many cases of obesity result from overconsumption of a diet high in fat. Excess dietary fat increases both adipose and non-adipose tissue lipid content, and through lipotoxicity leads to cell dysfunction and death. High dietary fat intake, with or without the development of obesity, impairs female hypothalamic-pituitary-ovarian (HPO) axis functionality and fertility...
June 6, 2017: Endocrinology
https://www.readbyqxmd.com/read/28582574/a-genetic-model-to-study-increased-hexosamine-biosynthetic-flux
#19
Sarah E Hugo, Amnon Schlegel
Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. Larvae showed increased triacylglycerol in the absence of other obvious defects. When we attempted to raise these otherwise normal appearing mutants to adulthood, we observed a developmental arrest and death in the early juvenile period. Here we report the positional cloning of the hmn locus and characterization of the defects caused by the mutation. Using bulk segregant analysis, fine mapping, and immunoblot assays we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) Glutamine-fructose-6-phosphate transamidase (Gfpt1)...
June 5, 2017: Endocrinology
https://www.readbyqxmd.com/read/28582497/protective-role-of-complement-c3-against-cytokine-mediated-%C3%AE-cell-apoptosis
#20
Reinaldo S Dos Santos, Laura Marroqui, Fabio A Grieco, Lorella Marselli, Mara Suleiman, Stefan R Henz, Piero Marchetti, Rasmus Wernersson, Decio L Eizirik
Type 1 diabetes is a chronic autoimmune disease characterized by pancreatic islet inflammation and â-cell destruction by proinflammatory cytokines and other mediators. Based on RNA sequencing and protein-protein interaction analyses of human islets exposed to proinflammatory cytokines, we identified complement C3 as a hub for some of the effects of cytokines. The proinflammatory cytokines interleukin-1â + interferon-γ increase C3 expression in rodent and human pancreatic â-cells and C3 is detected by histology in and around the islets of diabetic patients...
June 5, 2017: Endocrinology
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