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J Clin Invest. 2006 Mar;116(3):760-8.

Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature.

Author information

1
INSERM, U654, Centre Hospitalier Universitaire Henri-Mondor, Créteil, France. jacques.pantel@im3.inserm.fr

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.

PMID:
16511605
PMCID:
PMC1386106
DOI:
10.1172/JCI25303
[Indexed for MEDLINE]
Free PMC Article

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