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1{alpha},25-Dihydroxyvitamin D3 and Its TX527 Analog Inhibit the Growth of Endothelial Cells Transformed by Kaposi Sarcoma-Associated Herpes Virus G Protein-Coupled Receptor in Vitro and in Vivo.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, we have demonstrated that 1alpha,25(OH)2D3 and its TX527 analog have antiproliferative effects on the growth of endothelial cells transformed by the vGPCR in vitro and in vivo, the vitamin D receptor being part of the inhibitory mechanism of action. PMID: 19915163 [PubMed - as supplied by publisher] (Source: Endocrinology)
Source: Endocrinology - November 13, 2009 Category: Endocrinology Authors: Gonzalez-Pardo V, Martin D, Gutkind JS, Verstuyf A, Bouillon R, Russo de Boland A, Boland RL Tags: Endocrinology Source Type: journals

Meal-Anticipatory Glucagon-Like Peptide-1 Secretion in Rats.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Animals anticipating a meal initiate a series of responses enabling them to better cope with the meal's metabolic impact. These responses, such as cephalic insulin, occur prior to the onset of ingestion and are especially evident in animals maintained on a meal-feeding schedule with limited but predictable access to food each day. We tested the hypothesis that meal-fed rats secrete the incretin hormone glucagon-like peptide-1 (GLP-1) cephalically when anticipating a large meal. Male Long-Evans rats were fed ad libitum (controls) or adapted to a schedule on which food was available for the same 4-h period each day (meal...
Source: Endocrinology - November 13, 2009 Category: Endocrinology Authors: Vahl TP, Drazen DL, Seeley RJ, D'Alessio DA, Woods SC Tags: Endocrinology Source Type: journals

High Glucose Potentiates Collagen Synthesis and Bone Morphogenetic Protein-2-Induced Early Osteoblast Gene Expression in Rat Spinal Ligament Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, high glucose, via production of reactive oxygen species, subsequent activation of PKC, and inhibition of p38, enhances type I collagen synthesis and expression of early osteogenesis genes induced by BMP-2 in rat spinal ligament cells. Hyperglycemia may play an important role in the onset or progression of ossification of the posterior longitudinal ligament by promoting the responsiveness of ligament cells to osteogenic differentiation. PMID: 19915165 [PubMed - as supplied by publisher] (Source: Endocrinology)
Source: Endocrinology - November 13, 2009 Category: Endocrinology Authors: Li H, Jiang LS, Dai LY Tags: Endocrinology Source Type: journals

The Deletion Variant of Nicotinamide Nucleotide Transhydrogenase (Nnt) Does Not Affect Insulin Secretion or Glucose Tolerance.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The C57BL/6J (B6J) strain is the most widely used mouse strain in metabolic research. B6J mice produce a truncated form of nicotinamide nucleotide transhydrogenase (NNT), an enzyme that pumps protons across the inner mitochondrial membrane. It has been proposed that this results in B6J mice having reduced insulin secretion and glucose intolerance compared with other strains of mice (e.g. C3H/HeH and DBA/2) that have a full-length NNT. The aim of this study was to determine whether truncated NNT was associated with reduced insulin secretion and glucose intolerance, comparing B6 substrains that differ in having a truncat...
Source: Endocrinology - November 11, 2009 Category: Endocrinology Authors: Wong N, Blair AR, Morahan G, Andrikopoulos S Tags: Endocrinology Source Type: journals

Tissue-Selective Regulation of Aromatase Expression by Calcitriol: Implications for Breast Cancer Therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Aromatase, the enzyme that catalyzes estrogen synthesis, is critical for the progression of estrogen receptor-positive breast cancer (BCa) in postmenopausal women. We show that calcitriol, the hormonally active form of vitamin D, regulates the expression of aromatase in a tissue-selective manner. Calcitriol significantly decreased aromatase expression in human BCa cells and adipocytes and caused substantial increases in human osteosarcoma cells (a bone cell model exhibiting osteoblast phenotype in culture) and modest increases in ovarian cancer cells. Calcitriol administration to immunocompromised mice bearing human BC...
Source: Endocrinology - November 11, 2009 Category: Endocrinology Authors: Krishnan AV, Swami S, Peng L, Wang J, Moreno J, Feldman D Tags: Endocrinology Source Type: journals

Lysophosphatidic Acid Up-Regulates Expression of Growth-Regulated Oncogene-{alpha}, Interleukin-8, and Monocyte Chemoattractant Protein-1 in Human First-Trimester Trophoblasts: Possible Roles in Angiogenesis and Immune Regulation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined the expression of LPA receptors in primary culture of trophoblasts and the tissue. The effects of LPA on the expressions of chemokines of trophoblasts were examined using RT-PCR and enzyme immunoassay. We delineate signal pathways of LPA-inducing relevant chemokines in trophoblasts. The secretory chemokines were tested for angiogenic function using human endometrial microvascular endothelial cells and for immunological chemotaxis using decidual natural killer cells and THP-1 monocytes. The results revealed the expression of LPA1 receptors in trophoblast cells. LPA enhanced growth-regulated oncogene (GRO)-alpha,...
Source: Endocrinology - November 11, 2009 Category: Endocrinology Authors: Chen SU, Chou CH, Chao KH, Lee H, Lin CW, Lu HF, Yang YS Tags: Endocrinology Source Type: journals

Expression of Uncoupling Protein 1 in Mouse Brown Adipose Tissue Is Thyroid Hormone Receptor-{beta} Isoform Specific and Required for Adaptive Thermogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cold-induced adaptive (or nonshivering) thermogenesis in small mammals is produced primarily in brown adipose tissue (BAT). BAT has been identified in humans and becomes more active after cold exposure. Heat production from BAT requires sympathetic nervous system stimulation, T3, and uncoupling protein 1 (UCP1) expression. Our previous studies with a thyroid hormone receptor-beta (TRbeta) isoform-selective agonist demonstrated that after TRbeta stimulation alone, adaptive thermogenesis was markedly impaired, although UCP-1 expression in BAT was normal. We used mice with a dominant-negative TRbeta PV mutation (frameshif...
Source: Endocrinology - November 11, 2009 Category: Endocrinology Authors: Ribeiro MO, Bianco SD, Kaneshige M, Schultz JJ, Cheng SY, Bianco AC, Brent GA Tags: Endocrinology Source Type: journals

Rikkunshito Ameliorates the Aging-Associated Decrease in Ghrelin Receptor Reactivity via Phosphodiesterase III Inhibition.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we sought to clarify changes in peripheral and central appetite-related factors in aged mice. Furthermore, we investigated the effects of rikkunshito, a traditional Japanese medicine, on age-related anorexia. C57BL/6J mice that were 6 or 75 wk old were studied. We investigated changes in food intake, ghrelin and leptin levels, and the expression of appetite-related genes with age. In addition, we verified the effects of ghrelin, rikkunshito, phosphodiesterase 3 (PDE3), and phosphoinositide 3-kinase inhibitors on appetite. Food intake was significantly decreased in 75-wk-old mice compared with the 6-wk-old mi...
Source: Endocrinology - November 11, 2009 Category: Endocrinology Authors: Takeda H, Muto S, Hattori T, Sadakane C, Tsuchiya K, Katsurada T, Ohkawara T, Oridate N, Asaka M Tags: Endocrinology Source Type: journals

Regulation of Steroidogenic Acute Regulatory Protein Transcription in Largemouth Bass by Orphan Nuclear Receptor Signaling Pathways.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The steroidogenic acute regulatory (StAR) protein mediates the rate-limiting step of mitochondrial transport of cholesterol for steroid biosynthesis. To investigate the regulation of this protein in lower vertebrates, we cloned the StAR coding region from large-mouth bass for analysis. Induction of the mRNA corresponded with increasing levels of plasma sex steroids in vivo. Cultures of largemouth bass ovarian follicles were exposed to dibutyryl cAMP (dbcAMP), a potent signaling molecule for steroidogenesis. StAR mRNA expression was significantly up-regulated by dbcAMP signaling, suggesting that the 5' regulatory region...
Source: Endocrinology - November 11, 2009 Category: Endocrinology Authors: Kocerha J, Prucha MS, Kroll KJ, Steinhilber D, Denslow N Tags: Endocrinology Source Type: journals

Green Tea Polyphenol Epigallocatechin Gallate Reduces Endothelin-1 Expression and Secretion in Vascular Endothelial Cells: Roles for AMP-Activated Protein Kinase, Akt, and FOXO1.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Epigallocatechin gallate (EGCG), a green tea polyphenol, promotes vasodilation by phosphatidylinositol 3-kinase-dependent activation of Akt and endothelial nitric oxide synthase to stimulate production of nitric oxide. Reduction in endothelin-1 (ET-1) synthesis may also increase bioavailability of nitric oxide. We hypothesized that the phosphatidylinositol 3-kinase-dependent transcription factor FOXO1 may mediate effects of EGCG to regulate expression of ET-1 in endothelial cells. EGCG treatment (10 muM, 8 h) of human aortic endothelial cells reduced expression of ET-1 mRNA, protein, and ET-1 secretion. We identified a...
Source: Endocrinology - November 3, 2009 Category: Endocrinology Authors: Reiter CE, Kim JA, Quon MJ Tags: Endocrinology Source Type: journals

Rerouting of a Follicle-Stimulating Hormone Analog to the Regulated Secretory Pathway.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
LH and FSH are produced by the same gonadotrope cells of the anterior pituitary but differ in their mode of secretion. This coordinated secretion of LH and FSH is essential for normal follicular development and ovulation in females and for spermatogenesis in males. The structural signals encoded in the LH and FSH subunits that govern the intracellular sorting of LH through the regulated secretory pathway and FSH through the constitutive pathway are largely unknown. Our laboratory recently identified the seven amino acid carboxy tail of LHbeta as a sorting signal for LH in GH3 cells. Here we compared the morphological f...
Source: Endocrinology - November 3, 2009 Category: Endocrinology Authors: Pearl CA, Jablonka-Shariff A, Boime I Tags: Endocrinology Source Type: journals

Minireview: Transgenerational Inheritance of the Stress Response: A New Frontier in Stress Research.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It is well established in animal models that the prenatal environment can have a major impact on stress axis function throughout life. These changes can predispose to various metabolic, cardiovascular, and neurobiological pathophysiologies. Emerging evidence indicates that the same programming effects occur in humans. It is now becoming clear that the pathophysiological effects are not confined to the first-generation offspring and that there is transgenerational memory of fetal experience that can extend across multiple generations. The complex mechanisms by which transgenerational transmission of stress responsivenes...
Source: Endocrinology - November 3, 2009 Category: Endocrinology Authors: Matthews SG, Phillips DI Tags: Endocrinology Source Type: journals

Decreased Expression of A-Kinase Anchoring Protein 150 in GT1 Neurons Decreases Neuron Excitability and Frequency of Intrinsic Gonadotropin-Releasing Hormone Pulses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The frequency of intrinsic pulsatile GnRH secretion from endogenous GnRH neurons and GT1 GnRH cell lines is stimulated by increased intracellular cAMP levels. The downstream molecules comprising the cAMP signaling pathway are organized in microdomains by a family of scaffolding proteins, A-kinase anchoring proteins (AKAPs). These molecules tether protein kinase A, cAMP-specific phosphodiesterases, phosphatases to known substrates. In neurons AKAP150 organizes many of the signaling molecules known to regulate the excitability and intrinsic pulsatile activity of GnRH neurons. AKAP150 was expressed in both the GT1-1 and G...
Source: Endocrinology - November 3, 2009 Category: Endocrinology Authors: Chen Q, Weiner RI, Blackman BE Tags: Endocrinology Source Type: journals

Up-Regulation of Toll-Like Receptor 4/Nuclear Factor-{kappa}B Signaling Is Associated with Enhanced Adipogenesis and Insulin Resistance in Fetal Skeletal Muscle of Obese Sheep at Late Gestation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, our data show maternal obesity-induced inflammatory signaling in late gestation fetal muscle, which correlates with increased im adipogenesis and insulin resistance, which may predispose offspring to later-life obesity and diabetes. PMID: 19887565 [PubMed - as supplied by publisher] (Source: Endocrinology)
Source: Endocrinology - November 3, 2009 Category: Endocrinology Authors: Yan X, Zhu MJ, Xu W, Tong JF, Ford SP, Nathanielsz PW, Du M Tags: Endocrinology Source Type: journals

Central Insulin Signaling Is Attenuated by Long-Term Insulin Exposure via Insulin Receptor Substrate-1 Serine Phosphorylation, Proteasomal Degradation, and Lysosomal Insulin Receptor Degradation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Central insulin signaling is critical for the prevention of insulin resistance. Hyperinsulinemia contributes to insulin resistance, but it is not yet clear whether neurons are subject to cellular insulin resistance. We used an immortalized, hypothalamic, clonal cell line, mHypoE-46, which exemplifies neuronal function and expresses the components of the insulin signaling pathway, to determine how hyperinsulinemia modifies neuronal function. Western blot analysis indicated that prolonged insulin treatment of mHypoE-46 cells attenuated insulin signaling through phospho-Akt. To understand the mechanisms involved, time-cou...
Source: Endocrinology - November 3, 2009 Category: Endocrinology Authors: Mayer CM, Belsham DD Tags: Endocrinology Source Type: journals

Deletion of the Novel Oocyte-Enriched Gene, Gpr149, Leads to Increased Fertility in Mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Through in silico subtraction and microarray analysis, we identified mouse Gpr149, a novel, oocyte-enriched transcript that encodes a predicted orphan G-protein-coupled receptor (GPR). Phylogenetic analysis of GPR149 from fish to mammals suggests that it is widely conserved in vertebrates. By multitissue RT-PCR analysis, we found that Gpr149 is highly expressed in the ovary and also in the brain and the digestive tract at low levels. Gpr149 levels are low in newborn ovaries but increase throughout folliculogenesis. In the ovary, we found that granulosa cells did not express Gpr149, whereas germinal vesicle and meiosis ...
Source: Endocrinology - November 3, 2009 Category: Endocrinology Authors: Edson MA, Lin YN, Matzuk MM Tags: Endocrinology Source Type: journals

Peroxisome Proliferator-Activated Receptor-{alpha} Control of Lipid and Glucose Metabolism in Human White Adipocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This work aimed at characterizing the role of peroxisome proliferator-activated receptors (PPAR)alpha in human white adipocyte metabolism and at comparing PPARalpha and PPARgamma actions in these cells. Primary cultures of human fat cells were treated with the PPARalpha agonist GW7647 or the PPARgamma agonist rosiglitazone. Changes in gene expression were determined using DNA microrrays and quantitative RT-PCR. Western blot and metabolic studies were performed to identify the biological effects elicited by PPAR agonist treatments. GW7647 induced an up-regulation of beta-oxidation gene expression and increased palmitate...
Source: Endocrinology - November 3, 2009 Category: Endocrinology Authors: Ribet C, Montastier E, Valle C, Bezaire V, Mazzucotelli A, Mairal A, Viguerie N, Langin D Tags: Endocrinology Source Type: journals

Circadian Expression of Adiponectin and Its Receptors in Human Adipose Tissue.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Adiponectin is one of the most clinically relevant cytokines associated with obesity. However, circadian rhythmicity of adiponectin in human adipose tissue (AT) has not been analyzed. To assess whether the mRNA levels of adiponectin and its receptors (ADIPOR1 and ADIPOR2) might show daily circadian rhythms in visceral and sc fat explants obtained from morbid obese women, visceral and sc abdominal AT biopsies (n = 6) were obtained from morbidly obese women (body mass index >/=40 kg/m(2)). Anthropometric variables were measured and fasting plasma glucose, lipid, and lipoprotein concentrations were analyzed. To investi...
Source: Endocrinology - November 3, 2009 Category: Endocrinology Authors: Gómez-Abellán P, Gómez-Santos C, Madrid JA, Milagro FI, Campion J, Martínez JA, Ordovás JM, Garaulet M Tags: Endocrinology Source Type: journals

Wingless (Wnt)-3A Induces Trophoblast Migration and Matrix Metalloproteinase-2 Secretion through Canonical Wnt Signaling and Protein Kinase B/AKT Activation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Invasion of human trophoblasts is promoted through activation of wingless (Wnt) signaling, suggesting a role of the pathway in placental development and morphogenesis. However, details on the process such as involvement of canonical and/or noncanonical Wnt signaling cascades as well as their target genes are largely unknown. Hence, signal transduction via canonical Wnt signaling or phosphatidylinositide 3-kinase (PI3K)/AKT and their cross talk as well as trophoblast-specific protease expression were investigated in trophoblastic SGHPL-5 cells and primary extravillous trophoblasts purified from first-trimester placentas...
Source: Endocrinology - November 3, 2009 Category: Endocrinology Authors: Sonderegger S, Haslinger P, Sabri A, Leisser C, Otten JV, Fiala C, Knöfler M Tags: Endocrinology Source Type: journals

Different Degrees of Somatotroph Ablation Compromise Pituitary Growth Hormone Cell Network Structure and Other Pituitary Endocrine Cell Types.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We have generated transgenic mice with somatotroph-specific expression of a modified influenza virus ion channel, (H37A)M2, leading to ablation of GH cells with three levels of severity, dependent on transgene copy number. GH-M2(low) mice grow normally and have normal-size pituitaries but 40-50% reduction in pituitary GH content in adult animals. GH-M2(med) mice have male-specific transient growth retardation and a reduction in pituitary GH content by 75% at 42 d and 97% by 100 d. GH-M2(high) mice are severely dwarfed with undetectable pituitary GH. The GH secretory response of GH-M2(low) and GH-M2(med) mice to GH-rele...
Source: Endocrinology - November 3, 2009 Category: Endocrinology Authors: Waite E, Lafont C, Carmignac D, Chauvet N, Coutry N, Christian H, Robinson I, Mollard P, Le Tissier P Tags: Endocrinology Source Type: journals

Effects of TWEAK (TNF Superfamily Member 12) on Differentiation, Metabolism, and Secretory Function of Human Primary Preadipocytes and Adipocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Expansion of adipose tissue mass by hypertrophy and hyperplasia is the hallmark of obesity. An automated cDNA screen was established to identify secreted human proteins with an inhibitory effect on adipocyte differentiation and, thereby, a potential inhibitory effect on adipose tissue growth. A member of the TNF superfamily, TNF-like weak inducer of apoptosis (TWEAK; TNF superfamily 12) was identified by means of high-throughput screening with the lipophilic dye Nile Red as an inhibitor of murine adipocyte differentiation and, subsequently, also of human adipocyte differentiation. TWEAK inhibited lipid deposition in a ...
Source: Endocrinology - November 3, 2009 Category: Endocrinology Authors: Tiller G, Fischer-Posovszky P, Laumen H, Finck A, Skurk T, Keuper M, Brinkmann U, Wabitsch M, Link D, Hauner H Tags: Endocrinology Source Type: journals

Does finger fat produce sex differences in second to fourth digit ratios?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19846613 [PubMed - in process] (Source: Endocrinology)
Source: Endocrinology - October 24, 2009 Category: Endocrinology Authors: Wallen K Tags: Endocrinology Source Type: journals

Erratum.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Authors: PMID: 19846614 [PubMed - in process] (Source: Endocrinology)
Source: Endocrinology - October 24, 2009 Category: Endocrinology Tags: Endocrinology Source Type: journals

Evidence that Corticotropin-Releasing Hormone Modulates Myometrial Contractility during Human Pregnancy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, CRH at physiological concentrations acts synergistically with P4 contributing to myometrial quiescence. P4 withdrawal may reduce CRH-mediated relaxation. Our functional model does not support homologous or heterologous down-regulation of agonist-stimulated-cAMP pathways by high CRH concentrations. PDE inhibition potentiates CRH and salbutamol-induced relaxation. Up-regulation of PDEs, through chronic cAMP elevation by CRH, could provide a mechanism for down-regulation of agonist-stimulated-cAMP pathways at term. PMID: 19846610 [PubMed - as supplied by publisher] (Source: Endocrinology)
Source: Endocrinology - October 20, 2009 Category: Endocrinology Authors: Tyson EK, Smith R, Read M Tags: Endocrinology Source Type: journals

The Spontaneous Ala147Thr Amino Acid Substitution within the Translocator Protein Influences Pregnenolone Production in Lymphomonocytes of Healthy Individuals.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, our results demonstrate that the Ala147Thr spontaneous amino acid substitution within TSPO is able to affect pregnenolone production; this should encourage further studies to investigate its potential role in polygenic dyslipidemias. PMID: 19846611 [PubMed - as supplied by publisher] (Source: Endocrinology)
Source: Endocrinology - October 20, 2009 Category: Endocrinology Authors: Costa B, Pini S, Gabelloni P, Da Pozzo E, Abelli M, Lari L, Preve M, Lucacchini A, Cassano GB, Martini C Tags: Endocrinology Source Type: journals

Effects of Maternal Dexamethasone Treatment in Early Pregnancy on Pituitary-Adrenal Axis in Fetal Sheep.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Fetal exposure to elevated levels of bioactive glucocorticoids early in gestation, as in suspected cases of congenital adrenal hyperplasia, may result in adverse neurological events. Fetal hypothalamic-pituitary-adrenal development and function may be involved. We investigated immediate and long-term effects of maternal dexamethasone (DEX) administration early in pregnancy on fetal growth and pituitary-adrenal activity in sheep. Pregnant ewes carrying singleton fetuses (total n = 119) were randomized to control (2 ml saline/ewe) or DEX-treated groups (im injections of 0.14 mg/kg ewe weight |b1 12 h) at 40-41 d gestatio...
Source: Endocrinology - October 20, 2009 Category: Endocrinology Authors: Braun T, Li S, Sloboda DM, Li W, Audette MC, Moss TJ, Matthews SG, Polglase G, Nitsos I, Newnham JP, Challis JR Tags: Endocrinology Source Type: journals

Response to Carbohydrate and Fat Refeeding in the Expression of Genes Involved in Nutrient Partitioning and Metabolism: Striking Effects on Fibroblast Growth Factor-21 Induction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study aimed to assess the effects of carbohydrate (CHO) and fat intake on the expression of key genes related with nutrient partitioning and metabolism in main tissues involved in energy metabolism (white adipose tissue, liver, and skeletal muscle). Rats were studied under different conditions: feeding state, 24 h fasting, and 12 h refeeding after 24 h fasting with isocaloric amounts of CHO or fat. Fat, but not CHO, refeeding was associated with an increase in serum and liver triglyceride content. Main changes in gene expression elicited by CHO compared with fat refeeding were: 1) higher expression levels of genes rel...
Source: Endocrinology - October 15, 2009 Category: Endocrinology Authors: Sánchez J, Palou A, Picó C Tags: Endocrinology Source Type: journals

Forkhead Box O1/Pancreatic and Duodenal Homeobox 1 Intracellular Translocation Is Regulated by c-Jun N-Terminal Kinase and Involved in Prostaglandin E2-Induced Pancreatic {beta}-Cell Dysfunction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Prostaglandin E2 (PGE2) is a well-known mediator of beta-cell dysfunction in both type 1 and type 2 diabetes. We recently reported that down-regulation of the Akt pathway activity is implicated in PGE2-induced pancreatic beta-cell dysfunction. The aim of this study was to further dissect the signaling pathway of this process in pancreatic beta-cell line HIT-T15 cells and primary mouse islets. We found that PGE2 time-dependently increased the c-Jun N-terminal kinase (JNK) pathway activity. JNK inhibition by the JNK-specific inhibitor SP600125 reversed PGE2-inhibited glucose-stimulated insulin secretion (GSIS). PGE2 indu...
Source: Endocrinology - October 15, 2009 Category: Endocrinology Authors: Meng Z, Lv J, Luo Y, Lin Y, Zhu Y, Nie J, Yang T, Sun Y, Han X Tags: Endocrinology Source Type: journals

Androgens Induce Dopaminergic Neurotoxicity via Caspase-3-Dependent Activation of Protein Kinase C{delta}Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study examined the neurotoxic effects of androgens in a dopaminergic cell line (N27 cells) and the downstream signaling pathways activated by androgens. Treatment of N27 cells with testosterone- and dihydrotestosterone-induced mitochondrial dysfunction, protein kinase C (PKC)-delta cleavage, and apoptosis in dopaminergic neuronal cells. Inhibition of caspase-3 prevented the cleavage of PKCdelta from the full-length element to the catalytic fragment and apoptosis in N27 cells, suggesting that androgen-induced apoptosis is mediated by caspase-3-dependent activation of PKCdelta. Androgen-induced apoptosis may be specific...
Source: Endocrinology - October 15, 2009 Category: Endocrinology Authors: Cunningham RL, Giuffrida A, Roberts JL Tags: Endocrinology Source Type: journals

Brain-Endocrine Interactions: A Microvascular Route in the Mediobasal Hypothalamus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Blood-borne hormones acting in the mediobasal hypothalamus, like those controlling food intake, require relatively direct access to target chemosensory neurons of the arcuate nucleus (ARC). An anatomical substrate for this is a permeable microvasculature with fenestrated endothelial cells in the ARC, a system that has awaited comprehensive documentation. Here, the immunofluorescent detection of endothelial fenestral diaphragms in the rat ARC allowed us to quantitate permeable microvessels throughout its rostrocaudal extent. We have determined that permeable microvessels are part of the subependymal plexus irrigating ex...
Source: Endocrinology - October 15, 2009 Category: Endocrinology Authors: Ciofi P, Garret M, Lapirot O, Lafon P, Loyens A, Prévot V, Levine JE Tags: Endocrinology Source Type: journals

Expression of Guanylyl Cyclase (GC)-A and GC-B during Brain Development: Evidence for a Role of GC-B in Perinatal Neurogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Atrial (ANP) and C-type (CNP) natriuretic peptide generate physiological effects via selective activation of two closely related membrane receptors with guanylyl cyclase (GC) activity, known as GC-A and GC-B. As yet, however, the discrete roles for ANP/GC-A vs. CNP/GC-B signaling in many mammalian tissues are still poorly understood. We here used receptor affinity labeling and GC assays to characterize comparatively GC-A/GC-B expression and functional activity during rat brain development. The study revealed that GC-B predominates in the developing and GC-A in the adult brain, with regional differences each between cer...
Source: Endocrinology - October 15, 2009 Category: Endocrinology Authors: Müller D, Hida B, Guidone G, Speth RC, Michurina TV, Enikolopov G, Middendorff R Tags: Endocrinology Source Type: journals

Atrial Natriuretic Peptide Promotes Pancreatic Islet {beta}-Cell Growth and Akt/Foxo1a/Cyclin D2 Signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study shows that atrial natriuretic peptide (ANP) stimulates cell proliferation and [(3)H]thymidine incorporation in INS-1E glucose-sensitive rat beta-cell line cells and isolated rat islet DNA. In addition, cGMP, the second messenger of natriuretic peptide receptors (NPR) A and B, stimulated islet DNA biosynthesis. The NPR-A receptor was expressed in INS-1E cells and islets. ANP-stimulated INS-1E cell DNA biosynthesis was blocked by preincubation with LY294002 (50 muM), an inhibitor of phosphatidylinositol 3'-kinase (PI3K). An indicator of cell cycle progression, cyclin D2 mRNA was increased by 2- to 3-fold in ANP- o...
Source: Endocrinology - October 15, 2009 Category: Endocrinology Authors: You H, Laychock SG Tags: Endocrinology Source Type: journals

Mechanisms Involved in 3',5'-Cyclic Adenosine Monophosphate-Mediated Inhibition of the Ubiquitin-Proteasome System in Skeletal Muscle.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study was undertaken to investigate the role of beta2-adrenoceptors (AR) and cAMP in regulating the ubiquitin-proteasome system (UPS) in skeletal muscle. We report that increased levels of cAMP in isolated muscles, promoted by the cAMP phosphodiesterase inhibitor isobutylmethylxanthine was accompanied by decreased activity of the UPS, levels of ubiquitin-protein conjugates, and expression of atrogin-1, a key ubiquitin-protein ligase involved in muscle atrophy. In cultured myotubes, atrogin-1 induction after dexamethasone treatment was completely prevented by isobutylmethylxanthine. Furthermore, administration of clenb...
Source: Endocrinology - October 15, 2009 Category: Endocrinology Authors: Gonçalves DA, Lira EC, Baviera AM, Cao P, Zanon NM, Arany Z, Bedard N, Tanksale P, Wing SS, Lecker SH, Kettelhut IC, Navegantes LC Tags: Endocrinology Source Type: journals

Ubiquitin Carboxyl-Terminal Hydrolase L3 Promotes Insulin Signaling and Adipogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Insulin is a potent adipogenic hormone that triggers the induction of a series of transcription factors and specific proteins governing the differentiation of preadipocytes into mature adipocytes. Here we report that ubiquitin carboxyl-terminal hydrolase (UCH)-L3, a deubiquitinating enzyme, promotes insulin signaling and adipogenesis. Uchl3(-/-) mice had less visceral white adipose tissue compared with wild-type mice. In vitro adipogenesis experiments revealed that mouse embryonic fibroblasts (MEFs) and preadipocytes from Uchl3(-/-) mice had impaired ability to differentiate into mature adipocytes than those from wild-...
Source: Endocrinology - October 15, 2009 Category: Endocrinology Authors: Suzuki M, Setsuie R, Wada K Tags: Endocrinology Source Type: journals

The Cytokine Gene CXCL14 Restricts Human Trophoblast Cell Invasion by Suppressing Gelatinase Activity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, by using RT-PCR through human pregnancy, we found that CXCL14 was selectively expressed at early but not late pregnancy. Immunostaining revealed that CXCL14 proteins were strongly expressed in villous cytotrophoblasts and moderately in decidualized stromal cells but very weakly in syncytiotrophoblasts and extravillous trophoblasts. The effect of CXCL14 on trophoblast invasion were examined by using human villous explants cultured on Matrigel and further proved by invasion and migration assay of primary trophoblast cells and trophoblast cell line HTR-8/SVneo. Our data showed that CXCL14 significantly inhibite...
Source: Endocrinology - October 14, 2009 Category: Endocrinology Authors: Kuang H, Chen Q, Zhang Y, Zhang L, Peng H, Ning L, Cao Y, Duan E Tags: Endocrinology Source Type: journals

Adiponectin Expression Is Induced by Vitamin E via a Peroxisome Proliferator-Activated Receptor {gamma}-Dependent Mechanism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Adiponectin is a well-known adipokine secreted by adipocytes that presents insulin-sensitizing properties. The regulation of expression of this adipokine by micronutrients is largely unknown. We demonstrate here that adiponectin expression is induced in adipocytes after exposure to tocopherols via the peroxisome proliferator-activated receptor gamma (PPARgamma) pathway. Vitamin E force feeding resulted in an induction of adiponectin in mice at both mRNA and protein levels. Adiponectin mRNA and protein secretion were also increased by vitamin E (alpha- and gamma-tocopherol) in 3T3-L1 cells, together with PPARgamma mRNA,...
Source: Endocrinology - October 14, 2009 Category: Endocrinology Authors: Landrier JF, Gouranton E, Yazidi CE, Malezet C, Balaguer P, Borel P, Amiot MJ Tags: Endocrinology Source Type: journals

Growth Differentiation Factor-9 Mediates Follicle-Stimulating Hormone-Thyroid Hormone Interaction in the Regulation of Rat Preantral Follicular Development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
FSH regulates follicular growth in a stage-development fashion. Although preantral follicle stage is gonadotropin responsive, FSH is not required for preantral follicular growth. With the antrum, the follicles continue growing under the influence of FSH and become gonadotropin dependent. Although thyroid hormone is important for normal female reproductive function, its role and interaction with FSH in the regulation of preantral ovarian follicular growth is yet to be defined. In the present study, we have examined the action and interaction of FSH and T3 in the regulation of the growth of preantral follicles, especiall...
Source: Endocrinology - October 14, 2009 Category: Endocrinology Authors: Kobayashi N, Orisaka M, Cao M, Kotsuji F, Leader A, Sakuragi N, Tsang BK Tags: Endocrinology Source Type: journals

In Utero Exposure to Di-(2-Ethylhexyl) Phthalate Decreases Mineralocorticoid Receptor Expression in the Adult Testis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In utero exposure to di-(2-ethylhexyl) phthalate (DEHP) has been shown to result in decreased androgen formation by fetal and adult rat testes. In the fetus, decreased androgen is accompanied by the reduced expression of steroidogenic enzymes. The mechanism by which in utero exposure results in reduced androgen formation in the adult, however, is unknown. We hypothesized that deregulation of the nuclear steroid receptors might explain the effects of in utero DEHP exposure on adult testosterone production. To test this hypothesis, pregnant Sprague Dawley dams were gavaged with 100-950 mg DEHP per kilogram per day from g...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Martinez-Arguelles DB, Culty M, Zirkin BR, Papadopoulos V Tags: Endocrinology Source Type: journals

Kisspeptin Neurons in the Ovine Arcuate Nucleus and Preoptic Area Are Involved in the Preovulatory Luteinizing Hormone Surge.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Kisspeptin is the product of the Kiss1 gene that regulates GnRH secretion. In sheep, Kiss1 mRNA-expressing cells are found in the preoptic area (POA) and arcuate nucleus (ARC), and expression is up-regulated in the caudal ARC during the periovulatory period. We hypothesized that kisspeptin neurons in the ARC are activated by estradiol-17beta prior to the preovulatory LH surge. Ovariectomized ewes were treated as follows: 1) estradiol-17beta implants (sc 2 wk) to cause tonic negative feedback; 2) vehicle (no estrogen negative or positive feedback); or 3) positive feedback/GnRH surge-inducing injection of estradiol-17bet...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Smith JT, Li Q, Pereira A, Clarke IJ Tags: Endocrinology Source Type: journals

Smad1-Smad5 Ovarian Conditional Knockout Mice Develop a Disease Profile Similar to the Juvenile Form of Human Granulosa Cell Tumors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Granulosa cell tumors (GCTs) of the ovary are rare sex cord stromal tumors. Although generally indolent, GCTs recur, and if not diagnosed and treated in early stages, survival rates are significantly shortened. Very little is known regarding GCT etiology. Because of the low incidence of cases and lack of standard diagnostics, mouse models for granulosa cell tumors are a valuable tool for studying GCTs and provide models for developing diagnostic and treatment strategies. We recently developed a novel mouse model of metastatic granulosa cell tumors by genetic deletion of the bone morphogenetic protein signaling transcri...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Middlebrook BS, Eldin K, Li X, Shivasankaran S, Pangas SA Tags: Endocrinology Source Type: journals

Impact of Simvastatin on Adipose Tissue: Pleiotropic Effects in Vivo.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Statins belong to a class of drugs well known for their ability to reduce circulating low-density lipoprotein cholesterol. In addition to cholesterol lowering, they also exhibit potential antiinflammatory and antioxidant properties, suggesting that tissues other than liver may be targeted by statins to exert their beneficial metabolic effects. Adipocytes have received very little attention as a potential target of these drugs, possibly because adipocytes are not a major source of biosynthetic cholesterol. Here, we examine the effects of simvastatin on the secretory pathway, inflammation, and cellular metabolism of adip...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Khan T, Hamilton MP, Mundy DI, Chua SC, Scherer PE Tags: Endocrinology Source Type: journals

Free Fatty Acids Induce a Proinflammatory Response in Islets via the Abundantly Expressed Interleukin-1 Receptor I.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Islets of patients with type 2 diabetes mellitus (T2DM) display features of an inflammatory process including elevated levels of the cytokine IL-1beta, various chemokines, and macrophages. IL-1beta is a master regulator of inflammation, and IL-1 receptor type I (IL-1RI) blockage improves glycemia and insulin secretion in humans with T2DM and in high-fat-fed mice pointing to a pivotal role of IL-1RI activity in intra-islet inflammation. Given the association of dyslipidemia and T2DM, we tested whether free fatty acids (FFA) promote the expression of proinflammatory factors in human and mouse islets and investigated a ro...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Böni-Schnetzler M, Boller S, Debray S, Bouzakri K, Meier DT, Prazak R, Kerr-Conte J, Pattou F, Ehses JA, Schuit FC, Donath MY Tags: Endocrinology Source Type: journals

Fibroblast Growth Factor 21-Deficient Mice Demonstrate Impaired Adaptation to Ketosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Fibroblast growth factor 21 (FGF21) is a key metabolic regulator. Expressed primarily in liver and adipose tissue, FGF21 is induced via peroxisome proliferator-activated receptor (PPAR) pathways during states requiring increased fatty acid oxidation including fasting and consumption of a ketogenic diet. To test the hypothesis that FGF21 is a physiological regulator that plays a role in lipid oxidation, we generated mice with targeted disruption of the Fgf21 locus (FGF21 knockout). Mice lacking FGF21 had mild weight gain and slightly impaired glucose homeostasis, indicating a role in long-term energy homeostasis. Furthe...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Badman MK, Koester A, Flier JS, Kharitonenkov A, Maratos-Flier E Tags: Endocrinology Source Type: journals

Atypical Protein Kinase C Activity in the Hypothalamus Is Required for Lipopolysaccharide-Mediated Sickness Responses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
By activating the Toll-like receptor 4-nuclear factor-kappaB signal transduction pathway, the bacterial endotoxin lipopolysaccharide (LPS) induces anorexia, weight loss, fever, and other components of the sickness response. By comparison, the hormones leptin and insulin cause anorexia without sickness via a central mechanism involving the phosphatidylinositol-3 kinase signaling pathway. In the current study, we investigated whether a common Toll-like receptor 4 and phosphatidylinositol-3 kinase signaling intermediate, atypical protein kinase Czeta/lambda (aPKC), contributes to changes of energy balance induced by these...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Thaler JP, Choi SJ, Sajan MP, Ogimoto K, Nguyen HT, Matsen M, Benoit SC, Wisse BE, Farese RV, Schwartz MW Tags: Endocrinology Source Type: journals

Local Secretion of Urocortin 1 Promotes Microvascular Permeability during Lipopolysaccharide-Induced Inflammation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Urocortin1 (Ucn1) is a neuropeptide that regulates vascular tone and is implicated in both the vascular and immune cell-mediated responses to inflammation. The role of Ucn1 in regulating microvascular permeability has not been determined. We hypothesized that local Ucn1 release promotes microvascular permeability and that this effect augments the local gastrointestinal vascular response to lipopolysaccharide (LPS)-induced systemic inflammation. We measured hydraulic (Lp) and macromolecule permeability in mesenteric venules. We show that a continuous infusion of 10(-7) M Ucn1 in a postcapillary venule increased Lp 2-fol...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Cureton EL, Ereso AQ, Victorino GP, Curran B, Poole DP, Liao M, Harken AH, Bhargava A Tags: Endocrinology Source Type: journals

Phosphatidyl Inositol 3-Kinase Signaling in Hypothalamic Proopiomelanocortin Neurons Contributes to the Regulation of Glucose Homeostasis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent studies demonstrated a role for hypothalamic insulin and leptin action in the regulation of glucose homeostasis. This regulation involves proopiomelanocortin (POMC) neurons because suppression of phosphatidyl inositol 3-kinase (PI3K) signaling in these neurons blunts the acute effects of insulin and leptin on POMC neuronal activity. In the current study, we investigated whether disruption of PI3K signaling in POMC neurons alters normal glucose homeostasis using mouse models designed to both increase and decrease PI3K-mediated signaling in these neurons. We found that deleting p85alpha alone induced resistance to...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Hill JW, Xu Y, Preitner F, Fukuda M, Cho YR, Luo J, Balthasar N, Coppari R, Cantley LC, Kahn BB, Zhao JJ, Elmquist JK Tags: Endocrinology Source Type: journals

Cathepsin D Is the Primary Protease for the Generation of Adenohypophyseal Vasoinhibins: Cleavage Occurs within the Prolactin Secretory Granules.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Vasoinhibins are a family of N-terminal prolactin (PRL) fragments that inhibit blood vessel growth, dilation, permeability, and survival. The aspartyl endoprotease cathepsin D is active at acidic pH and can cleave rat PRL to generate vasoinhibins. We investigated whether and where vasoinhibins could be generated by cathepsin D in the adenohypophysis of rats and mice and whether their production could be gender dependent. Vasoinhibins were detected in primary cultures of rat adenohypophyseal cells by Western blot with antibodies directed against the N terminus of PRL but not the C terminus. Ovariectomized, estrogen-trea...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Cruz-Soto ME, Cosío G, Jeziorski MC, Vargas-Barroso V, Aguilar MB, Cárabez A, Berger P, Saftig P, Arnold E, Thebault S, Martínez de la Escalera G, Clapp C Tags: Endocrinology Source Type: journals

Growth Hormone-Releasing Peptide-2 Suppresses Vascular Oxidative Stress in ApoE-/- Mice But Does Not Reduce Atherosclerosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
GH-releasing peptide-2 (GHRP-2) is a synthetic peptide that increases circulating GH and IGF-I levels. It also binds to CD36, a scavenger receptor for oxidized low-density lipoprotein (OxLDL), and may prevent cellular uptake of this proatherogenic complex. To determine its potential antiatherogenic effects, GHRP-2 (20 mug twice daily) was administered sc to ApoE(-/-) mice for 12 wk. GHRP-2 increased circulating IGF-I 1.2- to 1.6-fold and decreased circulating interferon-gamma by 66%. Although GHRP-2 did not alter atherosclerotic plaque area, it decreased aortic production of superoxide as assessed by dihydroethidium st...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Titterington JS, Sukhanov S, Higashi Y, Vaughn C, Bowers C, Delafontaine P Tags: Endocrinology Source Type: journals

Inhibition of Oxygen-Induced Hypoxia-Inducible Factor-1{alpha} Degradation Unmasks Estradiol Induction of Vascular Endothelial Growth Factor Expression in ECC-1 Cancer Cells in Vitro.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Estradiol (E2) rapidly and strongly induces vascular endothelial growth factor (VEGF) transcription in uterine endometrial epithelial cells in vivo. We have shown that this is mediated by both the estrogen receptor-alpha and hypoxia-inducible factor (HIF)-1alpha. By contrast, E2 induces little or no VEGF expression in cultured breast or endometrial cancer cells, which lack HIF-1alpha due to the abnormally high concentration of oxygen ( approximately 20%) to which they are exposed. To test the hypothesis that restoring HIF-1alpha in cultured cells would restore the ability of E2 to induce VEGF expression, we treated hum...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Molitoris KH, Kazi AA, Koos RD Tags: Endocrinology Source Type: journals

Fingers as a Marker of Prenatal Androgen Exposure.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report the strongest evaluation of the value of 2D:4D as a biomarker for early androgen exposure. Individuals with 46,XY karyotype but no effective prenatal androgen exposure due to complete androgen insensitivity syndrome had digit ratios that were feminized: they were higher than those of typical men and similar to those of typical women. Nevertheless, the effect was modest in size, and there was considerable within-group variability and between-group overlap, indicating that digit ratio is not a good marker of individual differences in prenatal androgen exposure. PMID: 19819951 [PubMed - as supplied by publisher]...
Source: Endocrinology - October 8, 2009 Category: Endocrinology Authors: Berenbaum SA, Korman Bryk K, Nowak N, Quigley CA, Moffat S Tags: Endocrinology Source Type: journals