Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature.
J Clin Invest
; 116(3): 760-8, 2006 Mar.
Article
in En
| MEDLINE
| ID: mdl-16511605
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Body Height
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Mutation, Missense
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Receptors, G-Protein-Coupled
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Growth Disorders
Limits:
Adolescent
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Adult
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Animals
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Child
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
J Clin Invest
Year:
2006
Document type:
Article
Affiliation country:
France