Endocrine Abstracts

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The Thyrotropin receptor (TSHR) is known as the important key-player for regulation of thyroid growth and function. As a G-protein coupled receptor (GPCR) TSHR predominantly activates the Gs/adenylyl cyclase and the Gq/11 phospholipase C signaling pathways, that finally regulate thyroid hormone production. Aberrant thyroid hormone production can be caused by activating TSHR mutations in case of toxic thyroid nodules or non-autoimmune hyperthyroidism or via inactivating mutatio...

It is a widely accepted concept that G-protein-coupled receptors (GPCRs) are able to form homo- and heterodimers. The physiological relevance of these interactions is of utmost importance.Recently, we demonstrated that due to co-expression of two key players of hypothalamic body weight regulation, the melanocortin 3 receptor (MC3R) and ghrelin receptor (GHSR), signalling of the MC3R is enhanced (hyperstimulation) as compared to activation of MC3R alone. ...

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...

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...

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...

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...

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...

GPR83 is an orphan G-protein coupled receptor (GPCR) and is expressed in thymus and brain. Within the brain GPR83 mRNA is identified at high levels in the hypothalamic arcuate nucleus that is known to control for body weight regulation.Expression of GPR83 in the arcuate nucleus and the protection of GPR83 knock-out mice against diet induced obesity prompted us to investigate GPR83 signaling properties as well as potential interaction with the melanocorti...

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...