Endocrine Abstracts

The sequence–structure–function-analysis of glycoprotein hormone receptors (SSFA-GPHR) database provides a comprehensive set of mutation data for the glycoprotein hormone receptors (covering the lutropin – (LHCGR), the follitropin (FSHR) and the thyrotropin receptor (TSHR)). Numerous databases present functional information along with pooled data from various public resources, but tools to analyse the molecular effects of genetic variations are as yet poorly pro...

Activation of the human LH/CG receptor (LH/CGR) by lutropin (LH) and choriogonadotropin (CG) is essential in the human reproduction. Deletion of the Exon10 (LH/CGR-delExon10) resulting in a lack of 27 amino acids within the extracellular hinge-region of LH/CGR causes Leydig cell hypoplasia type II. To clarify why this deletion impairs LH but not CG action, we investigated the molecular determinants of LH/CGR activation elucidating the different behaviour of both hormones.<...

The aim of our study is to identify signalling sensitive residue positions of the glycoprotein hormone receptors (GPHR), especially the thyrotropin receptor (TSHR) on the transmembrane helices (TMH) 5 and 6, knowing to be involved in GPCR activation. We performed modelling driven site-directed mutagenesis to pinpoint residues that are responsible for stabilization of active and inactive conformations of the TSHR.We highlight two amino acids that are high...

G protein-coupled receptors (GPCRs) are critical for signal transduction within neuroendocrine signalling pathways, and genetic mutations in G protein-coupled GPCRs underlie numerous diseases. Inactivating GPCR mutations can impede ligand interactions or signal transduction, or can result in misfolding of nascent receptor proteins and subsequent retention in the endoplasmic reticulum (ER) and thus failure to traffic to the cell surface. Examination of the functionality and cel...

The human luteinizing hormone (LH)/choriogonadotropin (hCG) receptor (LHCGR) discriminates its two hormone ligands. LHCGR differs to the murine receptor (Lhr) in aminoacid residues potentially involved in qualitative discerning of LH and hCG, the latter absent in rodents. We aim to identify LHCGR residues involved in hCG/LH discrimination, indicating evolutionary determinants of human LH/hCG endocrine system. After comparing the LHCGR and Lhr sequences, we developed eight ...

The lutropin receptor (LHR) is associated with reproduction and becomes activated by choriogonadotropin (CG) or lutropin (LH) resulting in different physiological functions with regard to differing signaling cascades. The underlying mechanisms in receptor/hormone interaction are not yet understood. CG is known to induce trans-activation at LHR oligomers (activates a second receptor), but details of LH mechanisms were not clarified yet.To study this issue...