Article (Scientific journals)
Growth hormone releasing hormone excess and blockade in X-LAG syndrome.
Daly, Adrian; Lysy, Philippe; Defilles, Celine et al.
2016In Endocrine-Related Cancer
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Abstract :
[en] X-linked acrogigantism (X-LAG) syndrome is a newly-described form of inheritable pituitary gigantism that begins in early childhood and is usually associated with markedly elevated growth hormone (GH) and prolactin secretion by mixed pituitary adenomas/hyperplasia. Microduplications on chromosome Xq26.3 including the GPR101 gene cause X-LAG syndrome. In individual cases random GH-releasing hormone (GHRH) levels have been elevated. We performed a series of hormonal profiles in a young female sporadic X-LAG syndrome patient and subsequently undertook in vitro studies of primary pituitary tumor culture following neurosurgical resection. The patient demonstrated consistently elevated circulating GHRH levels throughout preoperative testing, which was accompanied by marked GH and prolactin hypersecretion; GH demonstrated a paradoxical increase following TRH administration. In vitro, the pituitary cells showed baseline GH and prolactin release that was further stimulated by GHRH administration. Co-incubation with GHRH and the GHRH receptor antagonist, acetyl-(D-Arg(2))-GHRH (1-29) amide, blocked the GHRH-induced GH stimulation; the GHRH receptor antagonist alone significantly reduced GH release. Pasireotide, but not octreotide, inhibited GH secretion. A ghrelin receptor agonist and an inverse agonist led to modest, statistically significant increases and decreases in GH secretion, respectively. GHRH hypersecretion can accompany the pituitary abnormalities seen in X-LAG syndrome. These data suggest that the pathology of X-LAG syndrome may include hypothalamic dysregulation of GHRH secretion, which is in keeping with localization of GPR101 in the hypothalamus. Therapeutic blockade of GHRH secretion could represent a way to target the marked hormonal hypersecretion and overgrowth that characterizes X-LAG syndrome.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Daly, Adrian  ;  Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Lysy, Philippe
Defilles, Celine
Rostomyan, Liliya  ;  Université de Liège - ULiège > Doct. sc. médicales (Bologne)
Mohamed, Amira
CABERG, Jean-Hubert ;  Centre Hospitalier Universitaire de Liège - CHU > Service de génétique
Raverot, Veronique
CASTERMANS, Emilie ;  Centre Hospitalier Universitaire de Liège - CHU > Service de génétique
Marbaix, Etienne
Maiter, Dominique
Brunelle, Chloe
Trivellin, Giampaolo
Stratakis, Constantine A.
BOURS, Vincent ;  Centre Hospitalier Universitaire de Liège - CHU > Service de génétique
Raftopoulos, Christian
Beauloye, Veronique
Barlier, Anne
BECKERS, Albert ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'endocrinologie clinique
More authors (8 more) Less
Language :
English
Title :
Growth hormone releasing hormone excess and blockade in X-LAG syndrome.
Publication date :
2016
Journal title :
Endocrine-Related Cancer
ISSN :
1351-0088
eISSN :
1479-6821
Publisher :
Society for Endocrinology, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 17 December 2015

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