Searchable abstracts of presentations at key conferences in endocrinology

ea0014s3.3 | Signaling and regulation of G-protein-coupled hormone receptors | ECE2007

Functional impact of GPCR heterodimerzation

Biebermann Heike

For over two decades the hypothesis of dimerization of G protein coupled receptors (GPCR) exist. But only in 1999 it became clear by investigation of GABA B receptors that dimerization is the prerequisite for function. Since then our understanding of GPCR function is widened by the fact that nearly all GPCRs form dimers or higher order oligomers. This formation of GPCR homodimers or heterodimers influence the functional properties of a GPCR from that we know of a monomer in it...

ea0041oc2.1 | Receptors & Signalling | ECE2016

3-T1AM signaling in the rat thyrocyte cell line PCCL3

Schanze Nancy , Khajavi Noushafarin , Mergler Stefan , Biebermann Heike , Kohrle Josef

The endogenous decarboxylated thyroid hormone (TH) metabolite 3-Iodothyronamine (3-T1AM) exerts partially TH antagonistic effects in rodents and was shown to suppress the hypothalamic pituitary thyroid axis in rats after single dose application. Therefore, it might play a role in maintaining TH homoeostasis. Among the molecular targets of 3-T1AM are G protein-coupled receptors like the trace amine associated receptor 1 (TAAR1) and adrenergic receptors. Furthermore, 3-T1AM was ...

ea0020p330 | Comparative Endocrinology | ECE2009

Comparative analyses between the glycoprotein-hormone receptors and the orphan leucine-rich repeat containing G-protein coupled receptor 4 (LGR4)

Kleinau Gunnar , Gruters Annette , Biebermann Heike , Krause Gerd

In recent decades intensive studies on the glycoprotein-hormone receptors (GPHRs) and their respective hormones have provided a number of molecular insights into the relationship between the structure and function of these proteins. This knowledge includes an understanding of hormone binding, of naturally occurring mutations nad mechanisms of signal transduction and G-protein binding processes.Together with the relaxin family peptide receptors (RxFP) the...

ea0020p680 | Signal Transduction | ECE2009

Identification of septin 3 as new protein-protein interaction partner of TrkB

Patrick Tarnow , Heike Gohler , Erich Wanker , Annette Gruters , Heike Biebermann

The melanocortin 4 receptor (MC4R) plays a prominent role in hypothalamic weight regulation. Activation of this receptor results by so far not understood mechanisms in a decrease of food-intake and an increase of energy expenditure. Recently a functional role downstream of MC4R signalling for brain derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B receptor (TrkB) was reported. TrkB signalling influences several neuronal processes like synapse for...

ea0016p529 | Obesity | ECE2008

Determination of dimerisation domains of the human melanocortin 4 receptor

Genetzky Jessica , Tarnow Patrick , Rediger Anne , Gruters Annette , Biebermann Heike

The melanocortin 4 receptor (MC4R), a G protein coupled receptor, has a prominent role in hypothalamic weight regulation. The MC4R was recently shown to form receptor dimers. The cannabinoid 1 receptor (CB1R) is the nearest phylogenetic relative of MC4R but fails to interact with the MC4R in vitro. In this study we aim to investigate receptor domains that are necessary for MC4R interaction. Four different chimeric receptors of MC4R and CB1R were constructed. The generated cons...

ea0020htb3 | Hot topics: Basic | ECE2009

Functional relevance of MC3R and GHSR heterodimerization in hypothalamic weight regulation

Rediger Anne , Tarnow Patrick , Gruters Annette , Schafer Michael , Strotmann Rainer , Schoneberg Torsten , Biebermann Heike

By a systematic approach we investigated the interaction of a selective number of GPCRs that are expressed in the arcuate nucleus and known to play an essential role in hypothalamic weight regulation. Based on the results of a sandwich ELISA and fluorescence resonance energy transfer (FRET) approach we report the interaction of the melanocortin three receptor (MC3R) and the growth hormone secretagogue receptor (GHSR) which are coexpressed on arcuate NPY/AgRP neurons. Fu...

ea0020p681 | Signal Transduction | ECE2009

A newly identified loss-of-function mutation in helix 5 reveals new insights into signalling mechanisms of the thyrotropin receptor

Winkler Franziska , Kleinau Gunnar , Gruters Annette , Krude Heiko , Krause Gerd , Biebermann Heike

In two siblings suffering from congenital hypothyroidism we identified a homozygous missence mutation Ala579Val in transmembrane helix 5 of the thyrotropin receptor (TSHR) gene which motivated us to investigate molecular details of this mutation.We were interested, firstly, in the functional effects regarding signal transduction and, secondly, in the particular structural properties of the wild type receptor and the Ala579Val mutant. The aim was to gain ...

ea0016oc2.1 | Thyroid | ECE2008

Analysis of early gene expression in mouse thyroid development

Hubner Caroline , Weber Martin , Biebermann Heike , Herrmann Bernhard , Gruters Annette , Krude Heiko

Background: Defective thyroid gland development occurs in 80% of congenital hypothyroidism (incidence of 1:3000–1:4000). Only <5% have been shown to be caused by molecular genetic defects in few transcription factor genes (Nkx2.1, Nkx2.5, Foxe1, Pax8, Hhex) which are known to play a role in thyroid gland development. Therefore, other genes with a critical role in early thyroid development are likely to be involved in the pathogenesis of thyroid dysgenesis.<p class...

ea0016oc2.2 | Thyroid | ECE2008

Identification of 25 novel NKX2-1 gene mutations in 100 patients with broad spectrum of brain and thyroid dysfunctions

Thorwarth Anne , Schnittert Sarah , Jyrch Sabine , Dame Christof , Biebermann Heike , Grueters Annette , Krude Heiko

Objective: The NKX2-1 gene, also known as TITF-1, TTF-1 or T/ebp, is a member of the homeodomain-containing NK-2 transcription factor gene family and expressed in early development of thyroid, lung and forebrain. Initial screening of patients with isolated congenital hypothyroidism failed to show mutations. The first human heterozygous deletion affecting the NKX2-1 gene to be reported was a neonate with respiratory failure, primary hypothyroidism and neurological signs matchin...

ea0016oc3.1 | Diabetes and obesity | ECE2008

Interaction of hypothalamic G-protein-coupled receptors (GPCRs) involved in weight regulation

Rediger Anne , Tarnow Patrick , Bickenbach Annika , Schafer Michael , Strotmann Rainer , Schoneberg Torsten , Gruters Annette , Biebermann Heike

Food intake is centrally regulated in hypothalamic nuclei. Peripheral hormonal signals activate their corresponding receptors in the arcuate nucleus (arc) and modulate the expression of pro-opiomelanocortin (POMC) and neuropetide Y (NPY)/agouti-related-protein (AgRP). Cleavage products of POMC stimulate melanocortin-4-receptors (MC4R) in the paraventricular nucleus (PVN) to inhibit food intake or stimulate MC3Rs in the arc to activate a feedback loop. Further mor...