title: Akt phosphorylation in lymphocytes provides an index of in vitro insulin-like growth factor I sensitivity associated with growth hormone-induced growth.
abstract: BACKGROUND
  Because IGF-I is the main mediator of GH action on osteogenic cells, individual differences in IGF-I sensitivity are expected to contribute to the variations of GH effects on growth. In GH-treated children, the variable responses in growth rates at a specific IGF-I target level indicate heterogeneity of responses to serum IGF-I exposures.
  
  
  OBJECTIVE
  This study tested a cell-based assay as an index of individual IGF-I sensitivity that could help dissect GH pharmacogenetics.
  
  
  METHODS
  Akt phosphorylation (P-Akt) was quantified in response to IGF-I in fresh lymphocytes from 50 short children (25 with idiopathic short stature and 25 born short for gestational age) whose growth parameters were being prospectively monitored during the first year of GH therapy (86 +/- 20 mug/kg.d).
  
  
  RESULTS
  Intra-individual triplicate measurements of IGF-I-stimulated P-Akt were reasonably consistent (0.11 < or = sd; mean < or = 0.23). Among the 50 children, the distribution of P-Akt in lymphocytes stimulated by 125 ng/ml IGF-I was closely associated with the growth response to GH administration (univariate P = 0.001). Both GH dosage (P = 0.006) and the fold increase in IGF-I levels (P = 0.04) in response to GH (P = 0.04) were also correlated with the growth response.
  
  
  CONCLUSIONS
  Lymphocytes are the only IGF-I target cells that can be easily studied in clinical research. IGF-I-stimulated P-Akt in these cells was found to be a predictor of GH efficacy, supporting a significant role of the first steps of IGF-I signaling in the individual variability of GH effects on growth.
authors.affiliation: Department of Pediatric Endocrinology, Saint Vincent de Paul Hospital, Paris V University, 75014 Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Lotton
authors.forename: Danielle
authors.initials: D
authors.lastname: Rodrigue
authors.forename: Caroline
authors.initials: C
authors.lastname: Elie
authors.forename: Anya
authors.initials: A
authors.lastname: Rothenbühler
authors.forename: Najiba
authors.initials: N
authors.lastname: Lahlou
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Stunff
authors.forename: Pierre
authors.initials: P
authors.lastname: Bougnères
mesh_terms: D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006128:Growth / Q000187:drug effects*; D019382:Human Growth Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt