Growth hormone resistance: clinical states and animal models

GH exerts pleiotropic effects on growth and metabolism through the GH recep tor. A deficiency in the GH receptor gene is thus associated with GH resist ance and dwarfism. Complete GH resistance in humans, or Laron syndrome, has been associated with numerous inherited defects in the GH receptor, includ ing point mutations, complete or partial gene deletions, and splice site al terations. Analysis of the GH receptor genes of these patients has provided considerable insight into structure-function relationships of the GH recep tor. However, the relative rarity of this disease and the obvious difficult ies involved in human research have prompted a search for an animal model o f GH resistance. Numerous models have been proposed, including the sex-link ed dwarf chicken, the guinea pig, and the Laron mouse. In this review, the characteristics and etiology of Laron syndrome and these animal models will be discussed. The insight provided by these disorders into the roles and m echanism of action of GH will also be reviewed.