Poster (Scientific congresses and symposiums)
SOMATOSTATIN ANALOGUE RESISTANCE IN X-LAG SYNDROME - IDENTIFICATION OF THE UNDERLYING MECHANISMS
Vandevoorde, Stéphanie; Abboud, Dayana; Laschet, Céline et al.
2019Spring meeting 2019 Belgian Society of Physiology and Pharmacology
 

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Abstract :
[en] INTRODUCTION | X-Linked Acro-Gigantism (X-LAG) Syndrome is a rare genetic disorder caused by a microduplication on the X-chromosome of an array of genes comprising gpr101. This disorder leads to a pituitary adenoma secreting high levels of growth hormone, via elevated cAMP levels inside the somatotrophs of the adenoma. However, X-LAG patients cannot be treated by somatostatin analogues (SSA), such as octreotide, and present only a minor decrease in cAMP in response to pasireotide. METHODS & RESULTS | In heterologously transfected GH3 cells, cAMP levels do not decrease in presence of GPR101 in response to SSA treatment because the coupling of Gαi-proteins to the somatostatin receptors expressed in the pituitary adenoma (i.e., SSTR2 and SSTR5) is decreased in presence of GPR101. Moreover, due to a decreased arrestin-coupling to SSTR2 in presence of GPR101, SSTR2 is less endocytosed after stimulation. CONCLUSION | GPR101 quenches the signalling pathways of SSTR2 and SSTR5. However, further studies are necessary to determine the underlying cause of the patients’ resistance to SSA
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Vandevoorde, Stéphanie ;  Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Abboud, Dayana  ;  Université de Liège - ULiège > Molecular Biology of Diseases-Molecular Pharmacology
Laschet, Céline
Daly, Adrian  ;  Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Hanson, Julien  ;  Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Beckers, Albert ;  Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Language :
English
Title :
SOMATOSTATIN ANALOGUE RESISTANCE IN X-LAG SYNDROME - IDENTIFICATION OF THE UNDERLYING MECHANISMS
Publication date :
May 2019
Event name :
Spring meeting 2019 Belgian Society of Physiology and Pharmacology
Event organizer :
PhysPhar Belgium
Event place :
Bruxelles, Belgium
Event date :
10 mai 2019
Available on ORBi :
since 08 June 2020

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