Ghrelin receptor mutations--too little height and too much hunger.
The ghrelin receptor is known from in vitro studies to signal in the absence of the hormone ghrelin at almost 50% of its maximal capacity. But, as for many other 7-transmembrane receptors, the in vivo importance of this ligand-independent signaling has remained unclear. In this issue of the JCI, Pantel et al. find that a natural mutation in the ghrelin receptor, Ala204Glu, which is associated with a selective loss of constitutive activity without affecting ghrelin affinity, potency, or efficacy, segregates in 2 families with the development of short stature (see the related article beginning on page 760). By combination of the observations from this study with those related to the phenotype of subjects carrying another natural ghrelin receptor mutation, Phe279Leu, having identical molecular-pharmacological properties, it is proposed that selective lack of ghrelin receptor constitutive signaling leads to a syndrome characterized not only by short stature, but also by obesity that apparently develops during puberty.
Holst
Birgitte
B
Laboratory for Molecular Pharmacology, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Schwartz
Thue W
TW
D019943:Amino Acid Substitution / Q000235:genetics*; D001827:Body Height / Q000235:genetics*; D054439:Ghrelin; D006801:Humans; D006815:Hunger / Q000502:physiology*; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D036361:Peptide Hormones / Q000378:metabolism*; D011627:Puberty / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D054440:Receptors, Ghrelin; D015398:Signal Transduction / Q000235:genetics; D013577:Syndrome
D054439:Ghrelin; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin