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- Title
Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature.
- Authors
Pantel, Jacques; Legendre, Marie; Cabrol, Sylvie; Hilal, Latifa; Hajaji, Yassir; Morisset, Séverine; Nivot, Sylvie; Vie-Luton, Marie-Pierre; Grouselle, Dominique; de Kerdanet, Marc; Kadiri, Abdelkrim; Epelbaum, Jacques; Le Bouc, Yves; Amselem, Serge
- Abstract
The growth hormone (GH) secretagogue receptor (GHSR) was cloned as the target of a family of synthetic molecules endowed with GH release properties. As shown recently through in vitro means, this receptor displays a constitutive activity whose clinical relevance is unknown. Although pharmacological studies have demonstrated that its endogenous ligand--ghrelin--stimulates, through the GHSR, GH secretion and appetite, the physiological importance of the GHSR-dependent pathways remains an open question that gives rise to much controversy. We report the identification of a GHSR missense mutation that segregates with short stature within 2 unrelated families. This mutation, which results in decreased cell-surface expression of the receptor, selectively impairs the constitutive activity of the GHSR, while preserving its ability to respond to ghrelin. This first description, to our knowledge, of a functionally significant GHSR mutation, which unveils the critical importance of the GHSR-associated constitutive activity, discloses an unusual pathogenic mechanism of growth failure in humans.
- Publication
The Journal of clinical investigation, 2006, Vol 116, Issue 3, p760
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI25303