Endocrine Abstracts

There are currently no curative treatments for metastatic pancreatic neuroendocrine tumours (PNETs), and the 5-year survival is <50%. Such tumours frequently have mutations in chromatin remodelling genes as well as the protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, menin, which is mutated in up to 40% of sporadic PNETs, and binds the histone methyltransferase MLL1. Histone modifications, and specifically acetylated residues on histone tail...

Context: Mitotane (1,1-dichloro-2-[o-chlorophenyl]-2-[p-chlorophenyl]ethane) is the only drug approved for treatment of adrenocortical carcinoma (ACC). Mitotane counteracts both tumor growth and tumoural steroid hormone production but treatment is severely hampered by unfavorable pharmacokinetics and serious side effects. Mitotane is a lipophilic compound and treatment emergent alterations of lipid metabolism are frequently observed. This raises the question whether mitotane d...

Background: Craniopharyngiomas are embryogenic malformations which lead to eating disorders and morbid obesity due to hypothalamic involvement. The experience with laparoscopic adjustable gastric banding (LAGB) in obese craniopharyngioma patients is limited especially in regard to long-term effects and tolerability.Patients and methods: We are reporting on four patients with childhood craniopharyngioma diagnosed at age 2, 13, 12, and 20 years.<p clas...

The classical model of GPCR activation entails the binding of a single ligand to a single receptor molecule, followed by transmembrane signal transduction to the appropriate G protein(s). The possibility of GPCRs functioning as dimers or oligomers still remains controversial, and is largely based on in vitro studies on transfected cells. The glycoprotein hormone receptors, including that of LH (LHCGR), differ from most GPCRs by their large extracellular ligand-binding...

Accepted dogma once stated that G protein-coupled receptors (GPCRs) function as monomers, however, over the last decade in vitro experiments have shown GPCRs to function as dimers and higher order oligomers. We have recently reported the first in vivo evidence for the physiological importance of Class A GPCR homodimerisation using the LHCGR as a model receptor. Transgenic co-expression of binding deficient LHCGR (LHCGR-LH) and signalling deficient ...

Hypothalamic obesity has major impact on prognosis and quality of life (QoL) in childhood craniopharyngioma (CP). The pathogenic relevance of initial hypothalamic involvement versus treatment-related hypothalamic lesions is a matter of controversy.One hundred and twenty patients were recruited prospectively during 2001 and 2007 and evaluated after 3 years of follow-up. Body mass index (BMI) and QoL at diagnosis and 36 mo after diagnosis were analyzed bas...

Background: Obesity is associated with macrophage infiltration of adipose tissue. These inflammatory cells affect adipocytes not only by classical cytokines but also by the secreted glycopeptide wnt5a. Healthy adipocytes on the other site are able to release the specific wnt5a inhibitor sFRP5. This protective effect, however, was found to be diminished in obesity. The aim of the present study was to examine i) whether obese human subjects exhibit increased serum concentrations...

Objective: Relationships of blood circulating melanocortins to childhood obesity are not well established. We evaluated serum α-melanocyte stimulating hormone (α-MSH) in lean children and different study groups of childhood obesity.Methods: We examined serum α-MSH in 52 otherwise healthy children with childhood obesity (Ob, mean age 11 years, 32 girls / 20 boys), 27 normal-weight children of same age, 7 additional obese patients with reduc...

Despite high survival rates (92%) in patients with childhood craniopharyngioma (CP), quality of life (QoL) is frequently impaired due to sequelae such as severe obesity resulting from hypothalamic involvement of CP. Based on the results of the multicenter prospective study KRANIOPHARYNGEOM 2000 radical surgery is no appropriate treatment strategy in patients with hypothalamic involvement. Furthermore, tumour progression/relapses are frequent early events in CP patients. The an...

G protein-coupled receptors (GPCRs) are one of the largest families of the mammalian genome, mediating the effects of approximately 40% of prescribed drugs. Until recently, accepted dogma stated that GPCRs exist as monomers, however, it is becoming evident that GPCRs can form higher order dimer/oligomer complexes which provide important mechanisms for the diversification of receptor function. The LHCGR is a class A family GPCR, primarily coupling to the Gαs pat...