Searchable abstracts of presentations at key conferences in endocrinology

ea0020oc5.1 | Thyroid: Basic and Clinical | ECE2009

Neurological and behavioral phenotypes in mice lacking Mct8-mediated neuronal T3 uptake

Schweizer Ulrich , Wirth Eva , Roth Stephan , Kohrle Josef , Gruters Annette

Thyroid hormone transport into cells critically depends on plasma membrane transport proteins. One of these, monocarboxylate transporter 8 (MCT8), is mutated in patients suffering from a form of X-linked mental retardation, the Allan-Herndon-Dudley syndrome. These patients are characterized by abnormal thyroid hormone and TSH plasma levels indicating a role for MCT8 in the regulation of the thyroid hormone axis. Mice lacking the Mct8 gene replicate the thyroid hormone a...

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...

ea0016p581 | Paediatric endocrinology | ECE2008

Successful treatment of isolated growth hormone deficiency type 1a with recombinant human growth hormone

Wessel Theda , Schnabel Dirk , Krude Heiko , Gruters Annette

Isolated growth hormone deficiency (IGHD) type 1a is caused by defects of the GH-I gene resulting in severe short stature. Treatment with growth hormone may become ineffective due to significant production of growth hormone antibodies. However, this has only been reported in patients treated with pituitary derived growth hormone. We present five cases with IGHD type 1a successfully treated with recombinant human growth hormone (rhGH).Five patients from f...

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...

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...