[en] GPR101 is an orphan G-protein coupled receptor with unknown ligand. In 2014, an international study clearly pointed to a strong association between this receptor and the X-linked acrogigantism (X-LAG) syndrome, which begins in childhood and causes the “tallest giants”. The children (carriers of the GPR101 duplication on the X chromosome) grow abnormally even before they are one year old, secrete phenomenal quantities of growth hormone, and develop pituitary adenomas that do not respond to current therapies. The mechanism by which GPR101 contributes to increased growth hormone secretion is currently not known. Nevertheless, the lack of mechanistic insight into the function of GPR101 precludes its validation as a drug target. This lack of knowledge on GPR101 is the consequence of the paucity of specific pharmacological/research tools currently available. Therefore, we propose to study GPR101 functions and its role in growth hormone regulation. First, we determined the receptor cellular localization. We also deciphered its constitutive signalling pathways by detecting high cAMP levels. We completed our study with an examination of receptor coupling to other pathways and G proteins. Furthermore, we applied targeted mutagenesis to modulate the receptor constitutive activity in order to understand the receptor function at a molecular level. These GPR101 mutants will help us to understand the role of this receptor in GH regulation and/or to treat people suffering from pituitary dysfunction. This information is an absolute prerequisite to link molecular pharmacology of GPR101 with physiological functions.
Research Center/Unit :
GIGA - molecular biology of disease
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Abboud, Dayana ; Université de Liège > Molecular Pharmacology- GIGA, Molecular Biology of Disease
Daly, Adrian ; Université de Liège > Département des sciences cliniques > Endocrinologie
Dupuis, Nadine ; Université de Liège > Département de pharmacie > Chimie pharmaceutique
Laschet, Céline ; Université de Liège > Département de pharmacie > Chimie pharmaceutique
Geubelle, Pierre ; Université de Liège > Département de pharmacie > Chimie pharmaceutique
Pirotte, Bernard ; Université de Liège > Département de pharmacie > Chimie pharmaceutique
BECKERS, Albert ; Centre Hospitalier Universitaire de Liège - CHU > Service d'endocrinologie clinique
Hanson, Julien ; Université de Liège > Département de pharmacie > Chimie pharmaceutique
Language :
English
Title :
GPR101 orphan GPCR: a novel cause of growth hormone deregulation
Publication date :
May 2017
Event name :
19th European Congress of Endocrinology
Event place :
Lisbon, Portugal
Event date :
du 20 mai 2017 au 23 mai 2017
Audience :
International
Name of the research project :
GPR101 orphan receptor: a novel cause of growth hormone deregulation
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] WBI - Wallonie-Bruxelles International [BE]