Endocrine Abstracts

So far it has been assumed that thyroid hormones -due to their lipophilicity- enter their target cells just by slipping through the membrane. After the initial description of a specific transport molecule for thyroid hormone in 2003 (Friesema et al. JBC) a new paradigm of thyroid hormone physiology has emerged. It turns out that as everything in nature, also the entering of thyroid hormone in its target cell is well regulated and the gate keeper is the MCT8 transporter, at lea...

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...

Obesity is a polymorphic chronic disease with epidemic prevalence. Furthermore, heritability of the weight phenotype is high. However, within the catabolic leptin–melanocortin signalling pathway, which is pivotal for body weight regulation, gene mutations are rare. This indicates that other, non-genetic heritable factors might play a role in the development of obesity, such as epigenetic mechanisms.In a candidate gene approach, we analyzed the funct...

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. ...

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...

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease resulting from adrenal unresponsiveness to ACTH. Patients present in early childhood with hyperpigmentation, hypoglycaemic episodes and seizures secondary to glucocorticoid deficiency. If left untreated this condition is fatal. Mineralocorticoid production is normal. Mutations in the ACTH receptor have been well described and account for approximately 25% of cases. We describe 3 additional novel mut...