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IL-1 β Inhibits Connexin 43 and Disrupts Decidualization of Human Endometrial Stromal Cells through ERK1/2 and p38 MAP Kinase.
We examined how IL-1β affects expression of the uterine gap junction protein, Cx43, which is known to be critical for embryonic implantation. We used an in vitro model of human endometrial stromal cells (ESC), Western blotting and a combination of validated, selective kinase inhibitors to evaluate five canonical IL-1β signaling pathways. Cx43 and two other markers of ESC differentiation (prolactin and VEGF) were inhibited predominantly via IL-1β-activated ERK1/2 and p38 MAP kinase cascades. The findings were corroborated using siRNA to silence critical genes in either pathway. By contrast, upregulation of endogenous pro...
Source: Endocrinology - September 11, 2017 Category: Endocrinology Authors: Yu J, Berga SL, Zou W, Yook DG, Pan JC, Andrade AA, Zhao L, Sidell N, Bagchi IC, Bagchi MK, Taylor RN Tags: Endocrinology Source Type: research

RAMP2 influences glucagon receptor pharmacology via trafficking and signaling.
Abstract 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 ef...
Source: Endocrinology - June 6, 2017 Category: Endocrinology Authors: Cegla J, Jones BJ, Gardiner JV, Hodson DJ, Marjot T, McGlone ER, Tan TM, Bloom SR Tags: Endocrinology Source Type: research

Transcription factor CREM mediates high glucose response in cardiomyocytes and in a male mouse model of prolonged hyperglycemia.
In conclusion, high glucose may alter the epigenetic landscape of cardiac cells. Sildenafil, restoring cGMP levels, counteracted the increase of CREM and Nexilin providing a protective effect in the presence of hyperglycemia. PMID: 28368536 [PubMed - as supplied by publisher]
Source: Endocrinology - March 22, 2017 Category: Endocrinology Authors: Barbati SA, Colussi C, Bacci L, Aiello A, Re A, Stigliano E, Isidori AM, Grassi C, Pontecorvi A, Farsetti A, Gaetano C, Nanni S Tags: Endocrinology Source Type: research

Hypoxia-inducible lipid droplet-associated (HILPDA) is not a direct physiological regulator of lipolysis in adipose tissue.
Abstract Triglycerides are stored in specialized organelles called lipid droplets. Numerous proteins have been shown to be physically associated with lipid droplets and govern their function. Previously, hypoxia-inducible lipid droplet-associated (HILPDA) was localized to lipid droplets and was suggested to inhibit triglyceride lipolysis in hepatocytes. We confirm the partial localization of HILPDA to lipid droplets and show that HILPDA is highly abundant in adipose tissue, where its expression is controlled by the peroxisome proliferator-activated receptor γ and by β-adrenergic stimulation. Levels of HILPDA mar...
Source: Endocrinology - March 17, 2017 Category: Endocrinology Authors: Dijk W, Mattijssen F, de la Rosa Rodriguez M, Loza Valdes A, Loft A, Mandrup S, Kalkhoven E, Qi L, Borst JW, Kersten S Tags: Endocrinology Source Type: research

Induction of Tissue Factor Pathway Inhibitor 2 by hCG regulates Periovulatory Gene Expression and Plasmin Activity.
Abstract A key event during the process of ovulation is an increased proteolytic activity that aids in breakdown of the follicular wall to permit oocyte release. How the activity of these proteases is regulated is still not known. We hypothesize that Tissue Factor Pathway Inhibitor 2 (TFPI2), a matrix-associated Kunitz-type serine protease inhibitor, plays a role in regulating proteolytic activity during the periovulatory period as in other tissues. TFPI2 is secreted into the extracellular matrix (ECM) where it is postulated to regulate physiological ECM remodeling. The expression profile of TFPI2 during the perio...
Source: Endocrinology - November 3, 2016 Category: Endocrinology Authors: Puttabyatappa M, Al-Alem LF, Zakerkish F, Rosewell KL, Brännström M, Curry TE Tags: Endocrinology Source Type: research

Cyclic AMP effectors regulate myometrial oxytocin receptor expression.
Abstract The factors that initiate human labor are poorly understood. We have tested the hypothesis that a decline in cAMP/PKA function leads to the onset of labor. Initially, we identified myometrial cAMP/PKA responsive genes (6 up-regulated and 5 down-regulated genes) and assessed their expression in myometrial samples taken from different stages of pregnancy and labor. We found that the oxytocin receptor (OTR) was one of the cAMP repressed genes and, given the importance of OTR in the labor process, we studied the mechanisms involved in greater detail using siRNA, chemical agonists and antagonists of the cAMP e...
Source: Endocrinology - September 26, 2016 Category: Endocrinology Authors: Yulia A, Singh N, Lei K, Sooranna SR, Johnson MR Tags: Endocrinology Source Type: research

The SMAD pathway is required for hepcidin response during endoplasmic reticulum stress.
In conclusion, our study indicates that hepcidin induction by ER stress involves the central regulatory SMAD1/5 pathway. PMID: 27483343 [PubMed - as supplied by publisher]
Source: Endocrinology - August 1, 2016 Category: Endocrinology Authors: Canali S, Vecchi C, Garuti C, Montosi G, Babitt JL, Pietrangelo A Tags: Endocrinology Source Type: research

Thyroid Hormone Receptor β (TRβ) Mediates Runt-Related Transcription Factor 2 (Runx2) Expression in Thyroid Cancer Cells: A novel signaling pathway in thyroid cancer.
Abstract Dysregulation of the thyroid hormone receptor β (TRβ) is common in human cancers. Restoration of functional TRβ delays tumor progression in models of thyroid and breast cancers implicating TRβ as a tumor suppressor. Conversely, aberrant expression of the runt-related transcription factor 2 (Runx2) is established in the progression and metastasis of thyroid, breast and other cancers. Silencing of Runx2 diminishes tumor invasive characteristics. With TRβ as a tumor suppressor and Runx2 as a tumor promoter, a compelling question is whether there is a functional relationship between these regulatory fact...
Source: Endocrinology - June 1, 2016 Category: Endocrinology Authors: Carr FE, Tai PW, Barnum MS, Gillis NE, Evans KG, Taber TH, White JH, Tomczak JA, Jaworski DM, Zaidi SK, Lian JB, Stein JL, Stein GS Tags: Endocrinology Source Type: research

Clock gene Bmal1 modulates human cartilage gene expression by crosstalk with Sirt1.
Abstract The critical regulation of peripheral circadian gene implicated in osteoarthritis (OA) has been recently recognized, however the causative role and clinical potential of the peripheral circadian rhythm attributable to such effects remains elusive. The purpose of this study was to elucidate the role of a circadian gene Bmal1 in human cartilage and pathophysiology of osteoarthritis. In our present study, the mRNA and protein levels of circadian rhythm genes, including NAD(+) and Sirt1 in human knee articular cartilage were determined. In OA cartilage, the levels of both Bmal1 and NAD(+) decreased significan...
Source: Endocrinology - June 1, 2016 Category: Endocrinology Authors: Yang W, Kang X, Liu J, Li H, Ma Z, Jin X, Qian Z, Xie T, Qin N, Feng D, Pan W, Chen Q, Sun H, Wu S Tags: Endocrinology Source Type: research

GATA4 regulates blood-testis barrier function and lactate metabolism in mouse Sertoli cells.
Abstract Conditional deletion of Gata4 in Sertoli cells (SCs) of adult mice has been shown to increase permeability of the blood-testis barrier (BTB) and disrupt spermatogenesis. To gain insight into the molecular underpinnings of these phenotypic abnormalities, we assessed the impact of Gata4 gene silencing in cell culture models. Microarray hybridization identified genes dysregulated by siRNA-mediated inhibition of Gata4 in TM4 cells, an immortalized mouse SC line. Differentially expressed genes were validated by qRT-PCR analysis of primary cultures of Gata4(flox/flox) mouse SCs that had been subjected to cre-me...
Source: Endocrinology - March 14, 2016 Category: Endocrinology Authors: Schrade A, Kyrönlahti A, Akinrinade O, Pihlajoki M, Fischer S, Rodriguez VM, Otte K, Velagapudi V, Toppari J, Wilson DB, Heikinheimo M Tags: Endocrinology Source Type: research

Multiple Transduction Pathways Mediate Thyrotropin Receptor Signaling in Preosteoblast-Like Cells.
Abstract It has been shown that the thyroid stimulating hormone (TSH) receptor (TSHR) couples to a number of different signaling pathways although the Gs-cAMP pathway has been considered primary. Herein we measured the effects of TSH on bone marker mRNA and protein expression in preosteoblast-like U2OS cells stably expressing TSHRs. We determined which signaling cascades are involved in the regulation of interleukin 11 (IL11), osteopontin (OPN), and alkaline phosphatase (ALPL). We demonstrated that TSH-induced upregulation of IL11 is primarily mediated via the Gs pathway as IL11 was upregulated by forskolin (FSK),...
Source: Endocrinology - March 7, 2016 Category: Endocrinology Authors: Boutin A, Neumann S, Gershengorn MC Tags: Endocrinology Source Type: research

Blockade of Sphingosine 1-Phosphate Receptor 2 Signaling Attenuates High-Fat Diet-Induced Adipocyte Hypertrophy and Systemic Glucose Intolerance in Mice.
Abstract Sphingosine 1-phosphate (S1P) is known to regulate insulin resistance in hepatocytes, skeletal muscle cells, and pancreatic β-cells. Among its five cognate receptors (S1pr1-5), S1P seems to counteract insulin signaling and confer insulin resistance via S1pr2 in these cells. S1P may also regulate insulin resistance in adipocytes, but the S1pr subtype(s) involved remains unknown. Here we investigated systemic glucose/insulin tolerance and phenotypes of epididymal adipocytes in high-fat diet-fed wild-type and S1pr2-deficient (S1pr2(-/-)) mice. Adult S1pr2(-/-) mice displayed smaller body/epididymal fat tiss...
Source: Endocrinology - March 4, 2016 Category: Endocrinology Authors: Kitada Y, Kajita K, Taguchi K, Mori I, Yamauchi M, Ikeda T, Kawashima M, Asano M, Kajita T, Ishizuka T, Banno Y, Kojima I, Chun J, Kamata S, Ishii I, Morita H Tags: Endocrinology Source Type: research

Urocortin 2 but not urocortin 3 promotes the synaptic formation in hipppocampal neurons via induction of NGF production by astrocytes.
Abstract Corticotropin-releasing hormone (CRH) family peptides play differential role during various physiological and pathophysiological responses, such as stress. Urocortins (UCNs) have been implicated to play complementary or contrasting actions for the effects of CRH during stress. It has been shown that activation of CRH receptor type 1 (CRHR1) results in decreased synapse formation in hippocampus. We therefore explored the effect of UCN2 and UCN3, the exclusive CRHR2 agonists, on synaptic formation in hippocampus. In hippocampal slices cultures, UCN2 but not UCN3 treatment increased the levels of presynaptic...
Source: Endocrinology - December 29, 2015 Category: Endocrinology Authors: Zheng Y, Zhang YM, Ni X Tags: Endocrinology Source Type: research

Endogenous IGFBP-3 mediates intrinsic apoptosis through modulation of Nur77 phosphorylation and nuclear export.
Abstract In non-transformed bovine mammary epithelial cells, the intrinsic apoptosis inducer anisomycin (ANS) induces IGFBP-3 expression and nuclear localization and knock-down of IGFBP-3 attenuates ANS-induced apoptosis. Others have shown in prostate cancer cells that exogenous IGFBP-3 induces apoptosis by facilitating nuclear export of the orphan nuclear receptor Nur77 and its binding partner retinoid X receptor-α (RXRα). The goal of the present work was to determine if endogenous IGFBP-3 plays a role in ANS-induced apoptosis by facilitating nuclear transport of Nur77 and/or RXRα in non-transformed cells. Kno...
Source: Endocrinology - September 4, 2015 Category: Endocrinology Authors: Agostini-Dreyer A, Jetzt AE, Stires H, Cohick WS Tags: Endocrinology Source Type: research

Type 2 Iodothyronine Deiodinase Activity is Required for Rapid Stimulation of PI3K by Thyroxine in Human Umbilical Vein Endothelial Cells.
Abstract Thyroid hormones (THs) exert a number of physiological effects on the cardiovascular system. Some of the nongenomic actions of 3,5,3`-triiodothyronine (T3) are achieved by cross-coupling of TH receptor (TR) to the phosphatidylinositol 3-kinase (PI3K)/protein kinase Akt (Akt) pathway. We observed that both T3 and thyroxine (T4) rapidly stimulated Akt phosphorylation and Ras-related C3 botulinum toxin substrate 1 (Rac1) activation, which resulted in cell migration, in a PI3K dependent manner in human umbilical vein endothelial cells (HUVECs). We identified the expression of type 2 iodothyronine deiodinase (...
Source: Endocrinology - August 18, 2015 Category: Endocrinology Authors: Aoki T, Tsunekawa K, Araki O, Ogiwara T, Nara M, Sumino H, Kimura T, Murakami M Tags: Endocrinology Source Type: research

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