Searchable abstracts of presentations at key conferences in endocrinology
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10th European Congress of Endocrinology

Poster Presentations

Signal transduction

ea0016p652 | Signal transduction | ECE2008

Insulin regulation of proliferation involves activation of akt and erk 1/2 signaling pathways in vascular smooth muscle cells

Isenovic Esma , Fretaud Maxenence , Koricanac Goran , Sudar Emina , Velebit Jelena , Dobutovic Branislava , Marche Pierre

This investigation used primary cultured rat vascular smooth muscle cells (VSMCs) to examine the effects of insulin (INS) on proliferation of VSMCs. In this study, protein kinase B (Akt) and p42/44 mitogen-activated protein kinase (ERK 1/2) signaling pathways in mediating the mitogenic actions of INS in VSMCs was investigated. Incubation of a rat VSMCs with INS (100 nM) for 10 min resulted in an increase of Akt phosphorylation by 6-fold (P<0.001) and ERK 1/2 phospho...

ea0016p653 | Signal transduction | ECE2008

The hinge region of the human TSH-receptor (hTSHR) mediates the activity of a superagonistic human TSH analog and bovine TSH

Mueller Sandra , Kleinau Gunnar , Skudlinski Mariusz , Jaeschke Holger , Krause Gerd , Paschke Ralf

The hinge region of the hTSHR links the extracellular LRR-domain with the transmembrane domain. Recently, we identified mutations E297A, E303A, and D382A in the hinge region with a cell surface expression comparable to the wt but with a strongly reduced bovine TSH (bTSH) binding. The combined triple mutation E297A/E303A/D382A revealed a cell surface expression comparable to the wt but in comparison to the single mutants a more pronounced reduction of bTSH binding (9% of the wt...

ea0016p654 | Signal transduction | ECE2008

Melatonin acts on pancreatic β-cells via melatonin receptors using the cAMP-, IP3- and probably also the cGMP-signalling pathway

Stumpf Ina , Muhlbauer Eckhard , Peschke Elmar

Physiological and molecular examinations provided evidence for the receptor-mediated influence of the pineal hormone melatonin on insulin secretion of pancreatic β-cells. The predominant effect is a reduction the rate of insulin secretion transmitted by downregulation of intracellular cAMP concentrations. In addition, there is also evidence for an activation of the PLC-IP3-pathway. Further investigations established the existence of the melatonin-receptor MT1, ...

ea0016p655 | Signal transduction | ECE2008

D327N SHBG is more effective than wild-type as modulator of estradiol signalling in breast cancer cells

Costantino Lucia , Catalano Maria Graziella , Frairia Roberto , Boccuzzi Giuseppe , Fortunati Nicoletta

Sex hormone-binding globulin (SHBG), the specific plasma carrier for sex steroids, regulates hormone bioavailable fraction and estrogen signalling system in breast cancer cells. A common single nucleotide polymorphism in the human SHBG gene results in an amino acid substitution (Asp327Asn), which introduces an additional N-glycosylation site that has been associated with reduced breast cancer risk in postmenopausal women. Since wild-type SHBG was demonstrated to interfe...

ea0016p656 | Signal transduction | ECE2008

Consequences of PRKAR1A (Carney complex gene) inactivation on cellular and subcellular PKA activity monitored by FRET-based reporters

Cazabat Laure , Ragazzon Bruno , Varin Audrey , Perlemoine Karine , Zhang Jin , Bertherat Jerome , Vandecasteele Gregoire

cAMP/PKA pathway activation is frequently involved in endocrine tumors with overactivity. The Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia syndrome which associates cardiac myxomas, spotty skin pigmentation and endocrine overactivity. Mutations in the PRKAR1A gene located at 17q22-24 and encoding for the R1A regulatory subunit of protein kinase A have been found in about 60% of CNC. These mutations are heterozygous germline mutations leading to ab...

ea0016p657 | Signal transduction | ECE2008

Orexins stimulate steroidogenic acute regulatory (StAR) protein expression through multiple signalling pathways

Ramanjaneya Manjunath , Conner Alex , Chen Jing , Lehnert Hendrik , Stanfield Peter , Randeva Harpal

Orexins mediate a variety of physiological processes including feeding behaviour, the circadian pathway and cortisol secretion. Steroidogenesis is regulated by a variety of neuropeptides and one of the key rate-limiting steps is cholesterol transport across the mitochondrial membrane by the steroidogenic acute regulatory (StAR) protein. StAR expression can be regulated through several different signalling pathways. Despite the clear link between orexins and steroid production,...

ea0016p658 | Signal transduction | ECE2008

G protein coupling and adenylyl cyclase inhibition are mediated by the DRY motif in the second intracellular domain of the SST5 receptor

Peverelli Erika , Lania Andrea , Mantovani Giovanna , Bondioni Sara , Beck-Peccoz Paolo , Spada Anna

Somatostatin exerts inhibitory effects on hormone secretion and cell proliferation by interacting with five different receptors (SST1–SST5) linked to effector systems via G proteins. The receptor structural domains mediating these effects have not been identified. Since SS is the hypothalamic peptide that physiologically inhibits GH secretion, aim of this study was to investigate the molecular determinants mediating the interaction of the human SST5 with G proteins and su...

ea0016p659 | Signal transduction | ECE2008

Ligand-dependent internalization of somatostatin receptors

van Vugt Harmke H , Schmid Herbert A , Sailer Andreas W

Somatostatin (somatotrophin release inhibiting factor; SRIF) is produced primarily in the hypothalamus and pancreas and inhibits the secretion of many hormones and neurotransmitters. Moreover, SRIF and SRIF analogs are able to inhibit tumor growth. Many human neuroendocrine and non-neuroendocrine tumors express the five known somatostatin receptors (sst1–5) in different amounts.Tachyphylaxis after prolonged treatment with octreotide (Sand...

ea0016p660 | Signal transduction | ECE2008

Combined rapamycin-octreotide treatment exerts its superior antiproliferative action by dramatically increasing p27/Kip1 expression

Cerovac Vesna , Stalla Gunter , Theodoropoulou Marily

Combined rapamycin-octreotide treatment has a stronger antiproliferative effect on non-functioning pituitary tumor cells compared with each drug alone. The mechanism of the combined treatment action was studied in AtT-20 pituitary tumor cells. Rapamycin is known to induce cell cycle arrest at the G1/S transition point. The entry of eukaryotic cells into the cell cycle is controlled primarily by the activation of cyclin-dependent kinases (CDK4/CDK6 and CDK2) by their respective...

ea0016p661 | Signal transduction | ECE2008

NOD proteins expression and function in the pituitary folliculostellate cells

Correa-de-Santana Eliane , Frohlich Bianca , Theodoropoulou Marily , Paez-Pereda Marcelo , Onofri Chiara , Labeur Martha , Renner Ulrich , Karl Stalla Gunter

Folliculostellate (FS) cells were found to regulate hormonal secretion in pituitary endocrine cells. This cell type share properties with components of the innate immune response such as dendritic cells and macrophages, and it is suggested that they are able to initiate immune responses and act as part of an immunoendocrine regulation system. Members of toll-like receptor (TLR) family recognize bacterial cell wall components and initiate an immune response. Recently, we detect...

ea0016p662 | Signal transduction | ECE2008

Corticotropin releasing hormone receptor signalling pathways and regulation of NOSIII activity in syncytialized BeWo cells

Delidaki Maria , Gu Mei , Vatish Manu , Grammatopoulos Dimitris

Placental corticotrophin releasing hormone (CRH) appears to play important physiological roles during pregnancy and labour. In the placenta, CRH appears to regulate diverse actions such as human trophoblast cell grown and invasion, tissue remodeling, direct modulation of the placental prostaglandin generation and bioavailability and control of placental vascular tone through regulation of endothelial NOS (NOSIII) expression and activation1. CRH actions are mediated ...

ea0016p663 | Signal transduction | ECE2008

Modulation of endothelial NF-κB transcription factors by carbohydrates

Blechmann Rebekka , Neulen Joseph , Motejlek Karin

Objectives: It is well known that compounds of follicular fluid, which is rich in carbohydrates, are able to regulate the expression of angiogenesis-related genes in endothelial cells. Nuclear factor κ B (NF-κB) transcription factors are important candidates in modulating the expression of these genes. The aim of our research is to determine if NF-κB factors are maybe involved in the regulation of endothelial angiogenesis-related genes and thus in ovarian angiog...

ea0016p664 | Signal transduction | ECE2008

cAMP/PKA and ERK1/2 dependent feedback mechanisms regulating type 2 CRH receptor signalling

Markovic Danijela , Punn Anu , Lehnert Hendrik , Grammatopoulos Dimitris

Corticotropin-releasing hormone (CRH) and its related peptides, the urocortins (UCNs) mediate their effects by binding to two types of GPCRs, CRH-R1 and CRH-R2. In most target tissues, the adenylyl cyclase/cAMP/PKA and the mitogen activated protein kinase (MAPK) are the two main pathways mediating the biological effects of CRH-Rs. For most multi-signal G-protein coupled receptors (GPCRs), there is considerable level of ‘cross-talk’ between different signalling cascad...

ea0016p665 | Signal transduction | ECE2008

Signalling properties of corticotropin-releasing hormone receptor (CRH-R1/2) in adrenal (H295R) cells

Punn Anu , Ramanjaneya Manjunath , Lehnert Hendrik , Grammatopoulos Dimitris

Corticotropin-releasing hormone (CRH) and urocortins (UCN) bind to two types of GPCRs (CRH-R1 and CRH-R2), activating a plethora of signalling cascades, including the mitogen-activated protein kinases (MAPKs) pathways. Although previous studies have identified that CRH directly regulates adrenal steroidogenesis1, the second messenger systems and downstream effectors remain poorly defined. The adrenal cell line H295R, which express both CRH-Rs1 was used to...