1. Academic Validation
  2. Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature

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

  • J Clin Invest. 2006 Mar;116(3):760-8. doi: 10.1172/JCI25303.
Jacques Pantel 1 Marie Legendre Sylvie Cabrol Latifa Hilal Yassir Hajaji Séverine Morisset Sylvie Nivot Marie-Pierre Vie-Luton Dominique Grouselle Marc de Kerdanet Abdelkrim Kadiri Jacques Epelbaum Yves Le Bouc Serge Amselem
Affiliations

Affiliation

  • 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.

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