Article (Scientific journals)
GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11
Abboud, Dayana; Daly, Adrian; Dupuis, Nadine et al.
2020In Nature Communications, 11 (1), p. 4752
Peer Reviewed verified by ORBi
 

Files


Full Text
s41467-020-18500-x.pdf
Publisher postprint (3.16 MB)
Download
Annexes
41467_2020_18500_MOESM1_ESM.pdf
(4.01 MB)
Download

Creative Commons License 4.0


All documents in ORBi are protected by a user license.

Send to



Details



Abstract :
[en] Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). Here, we report that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101 mice but without hyperplasia/tumorigenesis. We show that GPR101 constitutively activates not only Gs, but also Gq/11 and G12/13, which leads to GH secretion but not proliferation. These signatures of GPR101 signaling, notably PKC activation, are also present in human pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function.
Research center :
GIGA Molecular Biology of Diseases - ULiège
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
Disciplines :
Endocrinology, metabolism & nutrition
Genetics & genetic processes
Biochemistry, biophysics & molecular biology
Author, co-author :
Abboud, Dayana  ;  Université de Liège - ULiège > Molecular Biology of Diseases-Molecular Pharmacology
Daly, Adrian  ;  Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Dupuis, Nadine 
Bahri, Mohamed Ali  ;  Université de Liège - ULiège > CRC In vivo Imaging-Aging & Memory
Inoue, Asuka
Chevigné, Andy
Ectors, Fabien  ;  Université de Liège - ULiège > Scientifiques attachés au Doyen (F MV)
Plenevaux, Alain  ;  Université de Liège - ULiège > CRC In vivo Imaging-Preclinical Imaging
Pirotte, Bernard ;  Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Beckers, Albert ;  Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Hanson, Julien  ;  Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Language :
English
Title :
GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11
Publication date :
21 September 2020
Journal title :
Nature Communications
eISSN :
2041-1723
Publisher :
Nature Publishing Group, United Kingdom
Volume :
11
Issue :
1
Pages :
4752
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
GOLIATHS
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
ULiège - Université de Liège [BE]
CHU Liège - Centre Hospitalier Universitaire de Liège [BE]
WBI - Wallonie-Bruxelles International [BE]
Télévie [BE]
JABBS Foundation
Fondation Léon Fredericq [BE]
Available on ORBi :
since 01 October 2020

Statistics


Number of views
163 (35 by ULiège)
Number of downloads
147 (23 by ULiège)

Scopus citations®
 
30
Scopus citations®
without self-citations
21
OpenCitations
 
17

Bibliography


Similar publications



Contact ORBi