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Molecular and Cellular Endocrinology

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https://www.readbyqxmd.com/read/27908837/angiotensin-type-1a-receptor-regulates-%C3%AE-arrestin-binding-of-the-%C3%AE-2-adrenergic-receptor-via-heterodimerization
#1
András D Tóth, Pál Gyombolai, Bence Szalai, Péter Várnai, Gábor Turu, László Hunyady
Heterodimerization between angiotensin type 1A receptor (AT1R) and β2-adrenergic receptor (β2AR) has been shown to modulate G protein-mediated effects of these receptors. Activation of G protein-coupled receptors (GPCRs) leads to β-arrestin binding, desensitization, internalization and G protein-independent signaling of GPCRs. Our aim was to study the effect of heterodimerization on β-arrestin coupling. We found that β-arrestin binding of β2AR is affected by activation of AT1Rs. Costimulation with angiotensin II and isoproterenol markedly enhanced the interaction between β2AR and β-arrestins, by prolonging the lifespan of β2AR-induced β-arrestin2 clusters at the plasma membrane...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27908836/gq-and-gs-signaling-acting-in-synergy-to-control-glp-1-secretion
#2
Maria Hauge, Jeppe Pio Ekberg, Maja Storm Engelstoft, Pascal Timshel, Andreas N Madsen, Thue W Schwartz
GPR40 is generally known to signal through Gq. However, in transfected cells, certain synthetic agonists can make the receptor signal also through Gs and cAMP (Hauge et al., 2015). Here we find that, in colonic crypt cultures, the GLP-1 secretion induced by such Gq + Gs GPR40 agonists is indeed inhibited by blockers of both Gq and Gs and is eliminated by combining these. This in contrast to Gq-only GPR40 agonists which only are affected by the Gq inhibitor. Importantly, Gq-only GPR40 agonists in combination with low doses of selective synthetic agonists for Gs coupled receptors, e...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27908835/modulation-of-signaling-through-gpcr-camp-pka-pathways-by-pde4-depends-on-stimulus-intensity-possible-implications-for-the-pathogenesis-of-acrodysostosis-without-hormone-resistance
#3
Emmanuelle Motte, Catherine Le Stunff, Claire Briet, Nicolas Dumaz, Caroline Silve
In acrodysostosis without hormone resistance, a disease caused by phosphodiesterase (PDE)-4D mutations, increased PDE activity leads to bone developmental defects but with normal renal responses to PTH. To identify potential mechanisms for these disparate responses, we compared the effect of PDE activity on hormone signaling through the GPCR-Gsα-cAMP-PKA pathway in cells from two lineages, HEK-293 cells stably overexpressing PTH1R (HEKpthr) and human dermal fibroblasts, including studies evaluating cAMP levels using an Epac-based BRET-sensor for cAMP (CAMYEL)...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27908834/gamma-secretase-inhibitor-impairs-epithelial-to-mesenchymal-transition-induced-by-tgf-%C3%AE-in-ovarian-tumor-cell-lines
#4
M C Pazos, D Abramovich, A Bechis, P Accialini, F Parborell, M Tesone, G Irusta
Ovarian cancer is characterized by being highly metastatic, a feature that represents the main cause of failure of the treatment. This study investigated the effects of γ-secretase inhibition on the TGF-β-induced epithelial-mesenchymal transition (EMT) process in ovarian cancer cell lines. SKOV3 cells incubated in the presence of TGF-β showed morphological and biochemical changes related to EMT, which were blocked by co-stimulation with TGF-β and the γ-secretase inhibitor DAPT. In SKOV3 and IGROV1 cells, the co-stimulation blocked the cadherin switch and the increase in the transcription factors Snail, Slug, Twist and Zeb1 induced by TGF-β...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27899324/understanding-the-common-themes-and-diverse-roles-of-the-second-extracellular-loop-ecl2-of-the-gpcr-super-family
#5
Michael J Woolley, Alex C Conner
The extracellular loops (ECLs) of G protein-coupled receptors (GPCRs) can bind directly to docked orthosteric or allosteric ligands, they can contain transient contact points for ligand entry into the transmembrane (TM) bundle and they can regulate the activation of the receptor signalling pathways. Of the three ECLs, ECL2 is the largest and most structurally diverse reflecting its functional importance. This has been shown through biochemical techniques and has been supported by the many subsequent crystal structures of GPCRs bound to both agonists and antagonists...
November 26, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27894867/creatine-kinase-as-a-marker-of-obesity-in-a-multi-ethnic-population
#6
Yentl C Haan, Inge Oudman, Frederieke S Diemer, Fares A Karamat, Irene G van Valkengoed, Gert A van Montfrans, Lizzy M Brewster
OBJECTIVE: Creatine kinase (CK), the central regulatory enzyme of energy metabolism, is particularly high in type II skeletal muscle fibers, which are associated with insulin resistance and obesity. As resting plasma CK is mainly derived from skeletal muscle, we assessed whether plasma CK is associated with markers of obesity. METHODS: In this cross-sectional study, we analyzed a random sample of the multi-ethnic population of Amsterdam, the Netherlands, consisting of 1444 subjects aged 34-60 years...
November 25, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27890559/fluoxetine-and-its-active-metabolite-norfluoxetine-disrupt-estrogen-synthesis-in-a-co-culture-model-of-the-feto-placental-unit
#7
Andrée-Anne Hudon Thibeault, Laetitia Laurent, Sung Vo Duy, Sébastien Sauvé, Patrick Caron, Chantal Guillemette, J Thomas Sanderson, Cathy Vaillancourt
The effects of fluoxetine, one of the most prescribed selective serotonin-reuptake inhibitors (SSRIs) during pregnancy, and its active metabolite norfluoxetine were studied on placental aromatase (CYP19) and feto-placental steroidogenesis Fluoxetine did not alter estrogen secretion in co-culture of fetal-like adrenocortical (H295R) and trophoblast-like (BeWo) cells used as a model of the feto-placental unit, although it induced CYP19 activity, apparently mediated by the serotonin (5-HT) 2A receptor/PKC signalling pathway...
November 24, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27889473/endothelial-cells-regulate-%C3%AE-catenin-activity-in-adrenocortical-cells-via-secretion-of-basic-fibroblast-growth-factor
#8
Carolin Schwafertz, Sven Schinner, Markus C Kühn, Matthias Haase, Amelie Asmus, Birgit Mülders-Opgenoorth, Ishrath Ansurudeen, Peter J Hornsby, Henning Morawietz, Elke Oetjen, Matthias Schott, Holger S Willenberg
Endothelial cell-derived products influence the synthesis of aldosterone and cortisol in human adrenocortical cells by modulating proteins such as steroidogenic acute-regulatory (StAR) protein, steroidogenic factor (SF)-1 and CITED2. However, the potential endothelial cell-derived factors that mediate this effect are still unknown. The current study was perfomed to look into the control of β-catenin activity by endothelial cell-derived factors and to identify a mechanism by which they affect β-catenin activity in adrenocortical NCIH295R cells...
November 23, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27889472/comprehensive-assessment-of-estrogen-receptor-beta-antibodies-in-cancer-cell-line-models-and-tissue-reveals-critical-limitations-in-reagent-specificity
#9
Adam W Nelson, Arnoud J Groen, Jodi L Miller, Anne Y Warren, Kelly A Holmes, Gerard A Tarulli, Wayne D Tilley, Benita S Katzenellenbogen, John R Hawse, Vincent J Gnanapragasam, Jason S Carroll
Estrogen Receptor-β (ERβ) has been implicated in many cancers. In prostate and breast cancer its function is controversial, but genetic studies implicate a role in cancer progression. Much of the confusion around ERβ stems from antibodies that are inadequately validated, yet have become standard tools for deciphering its role. Using an ERβ-inducible cell system we assessed commonly utilized ERβ antibodies and show that one of the most commonly used antibodies, NCL-ER-BETA, is non-specific for ERβ. Other antibodies have limited ERβ specificity or are only specific in one experimental modality...
November 23, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27889471/functional-characterization-of-two-naturally-occurring-mutations-v-221-g-and-t-449-n-in-the-follicle-stimulating-hormone-receptor
#10
Antara A Banerjee, Swati K Achrekar, Shaini Joseph, Bhakti R Pathak, Smita D Mahale
Naturally occurring mutations in follicle stimulating hormone receptor (FSHR) affect the receptor function. Here, we characterized two such previously reported mutations, V(221)G and T(449)N, in the extracellular domain and transmembrane helix 3, of FSHR, respectively. Functional studies with the V(221)G mutant demonstrated an impairment in FSH binding and signaling. Validation of X-ray crystallography data indicating the contribution of FSHR specific residues in the vicinity of V(221) to contribute to FSH-FSHR interaction was carried out...
November 23, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27888004/unliganded-estrogen-receptor-alpha-regulates-vascular-cell-function-and-gene-expression
#11
Qing Lu, Gavin R Schnitzler, Caroline S Vallaster, Kazutaka Ueda, Stephanie Erdkamp, Christine E Briggs, Lakshmanan K Iyer, Iris Z Jaffe, Richard H Karas
The unliganded form of the estrogen receptor is generally thought to be inactive. Our prior studies, however, suggested that unliganded estrogen receptor alpha (ERα) exacerbates adverse vascular injury responses in mice. Here, we show that the presence of unliganded ERα decreases vascular endothelial cell (EC) migration and proliferation, increases smooth muscle cell (SMC) proliferation, and increases inflammatory responses in cultured ECs and SMCs. Unliganded ERα also regulates many genes in vascular ECs and mouse aorta...
November 22, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27888003/small-non-coding-rnas-based-bone-regulation-and-targeting-therapeutic-strategies
#12
Ying Yang, Sijie Fang
Small non-coding RNAs, which are 20-25 nucleotide ribonucleic acids, have emerged as an important transformation in the biological evolution over almost three decades. microRNAs (miRNAs) and short interfering RNAs (siRNAs) are two significant categories of the small RNAs that exert important effects on bone endocrinology and skeletology. Therefore, clarifying the expression and function of these important molecules in bone endocrine physiology and pathology is of great significance for improving their potential therapeutic value for metabolism-associated bone diseases...
November 22, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27888002/polymorphisms-in-mir499a-and-mir125a-gene-are-associated-with-autoimmune-thyroid-diseases
#13
TianTian Cai, Jie Li, Xiaofei An, Ni Yan, Danfeng Li, Yanfei Jiang, Wen Wang, Liangfeng Shi, Qiu Qin, Ronghua Song, Guofei Wang, Wenjuan Jiang, Jin-An Zhang
BACKGROUND: Single nucleotide polymorphisms (SNPs) of the miR-146a, miR-499a and miR-125a have been shown to be associated with the susceptibility to several autoimmune diseases. This study was conducted to identify the association of SNPs rs2910164, rs57095329, rs3746444 and rs12976445 with autoimmune thyroid diseases (AITDs) in a Chinese Han population. METHODS: We enrolled 1061 patients with AITDs, including 701 patients with Graves' disease (GD) and 360 patients with Hashimoto's thyroiditis (HT), and 938 healthy individuals for a case-control genetic association study...
November 22, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27884781/epigenetic-mechanisms-underlying-lifespan-and-age-related-effects-of-dietary-restriction-and-the-ketogenic-diet
#14
Cesar L Moreno, Charles V Mobbs
Aging constitutes the central risk factor for major diseases including many forms of cancer, neurodegeneration, and cardiovascular diseases. The aging process is characterized by both global and tissue-specific changes in gene expression across taxonomically diverse species. While aging has historically been thought to entail cell-autonomous, even stochastic changes, recent evidence suggests that modulation of this process can be hierarchal, wherein manipulations of nutrient-sensing neurons (e.g., in the hypothalamus) produce peripheral effects that may modulate the aging process itself...
November 21, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27884780/regulation-of-metabolic-health-and-aging-by-nutrient-sensitive-signaling-pathways
#15
Nicole E Cummings, Dudley W Lamming
All organisms need to be capable of adapting to changes in the availability and composition of nutrients. Over 75 years ago, researchers discovered that a calorie restricted (CR) diet could significantly extend the lifespan of rats, and since then a CR diet has been shown to increase lifespan and healthspan in model organisms ranging from yeast to non-human primates. In this review, we discuss the effects of a CR diet on metabolism and healthspan, and highlight emerging evidence that suggests that dietary composition - the precise macronutrients that compose the diet - may be just as important as caloric content...
November 21, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27876515/regenerative-therapy-for-hypothyroidism-mechanisms-and-possibilities
#16
Anthony N Hollenberg, Jinyoung Choi, Maria Serra, Darrell N Kotton
The ability to derive functional thyroid follicular cells from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) would provide potential therapeutic benefit for patients with congenital or post-surgical hypothyroidism. Furthermore, understanding the process by which thyroid follicular cells develop will also provide great insight into the key steps that regulate the development of other tissues derived from endoderm. Here we review the advances in our understanding of the process of thyroid follicular cell development including the creation of two models that have allowed for the rescue of hypothyroid mouse recipients through the transplantation of thyroid follicular cells derived from mouse ESCs...
November 19, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27856330/metformin-suppresses-adipogenesis-through-both-amp-activated-protein-kinase-ampk-dependent-and-ampk-independent-mechanisms
#17
Suet Ching Chen, Rebecca Brooks, Jessica Houskeeper, Shaun K Bremner, Julia Dunlop, Benoit Viollet, Pamela J Logan, Ian P Salt, S Faisal Ahmed, Stephen J Yarwood
People with Type 2 diabetes mellitus (T2DM) have reduced bone mineral density and an increased risk of fractures due to altered mesenchymal stem cell (MSC) differentiation in the bone marrow. This leads to a shift in the balance of differentiation away from bone formation (osteogenesis) in favour of fat cell development (adipogenesis). The commonly used anti-diabetic drug, metformin, activates the osteogenic transcription factor Runt-related transcription factor 2 (Runx2), which may suppress adipogenesis, leading to improved bone health...
November 14, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27845161/downregulation-of-autophagy-gene-expression-in-endometria-from-women-with-polycystic-ovary-syndrome
#18
Mirjana Sumarac-Dumanovic, Milica Apostolovic, Kristina Janjetovic, Danka Jeremic, Dusan Popadic, Aleksandar Ljubic, Jelena Micic, Jelena Dukanac-Stamenkovic, Aleksandra Tubic, Darko Stevanovic, Dragan Micic, Vladimir Trajkovic
Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling of the human endometrium. We investigated endometrial mRNA expression of 23 autophagy-related (ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1 (FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin B1), autophagosome elongation (ATG3, ATG5, γ-aminobutyric acid receptor-associated protein - GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were significantly reduced in anovulatory PCOS compared to healthy endometrium...
November 11, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27840174/activation-of-amp-activated-protein-kinase-rapidly-suppresses-multiple-pro-inflammatory-pathways-in-adipocytes-including-il-1-receptor-associated-kinase-4-phosphorylation
#19
Sarah J Mancini, Anna D White, Silvia Bijland, Claire Rutherford, Delyth Graham, Erik A Richter, Benoit Viollet, Rhian M Touyz, Timothy M Palmer, Ian P Salt
Inflammation of adipose tissue in obesity is associated with increased IL-1β, IL-6 and TNF-α secretion and proposed to contribute to insulin resistance. AMP-activated protein kinase (AMPK) regulates nutrient metabolism and is reported to have anti-inflammatory actions in adipose tissue, yet the mechanisms underlying this remain poorly characterised. The effect of AMPK activation on cytokine-stimulated proinflammatory signalling was therefore assessed in cultured adipocytes. AMPK activation inhibited IL-1β-stimulated CXCL10 secretion, associated with reduced interleukin-1 receptor associated kinase-4 (IRAK4) phosphorylation and downregulated MKK4/JNK and IKK/IκB/NFκB signalling...
November 11, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27838399/pancreas-%C3%AE-cell-regeneration-facultative-or-dedicated-progenitors
#20
Solomon Afelik, Meritxell Rovira
The adult pancreas is only capable of limited regeneration. Unlike highly regenerative tissues such as the skin, intestinal crypts and hematopoietic system, no dedicated adult stem cells or stem cell niche have so far been identified within the adult pancreas. New β cells have been shown to form in the adult pancreas, in response to high physiological demand or experimental β-cell ablation, mostly by replication of existing β cells. The possibility that new β cells are formed from other sources is currently a point of major controversy...
November 9, 2016: Molecular and Cellular Endocrinology
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