title: Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states.
abstract: BACKGROUND
  States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels.
  
  
  OBJECTIVE
  The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit.
  
  
  METHODS
  We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2-3 months of r-metHuLeptin treatment.
  
  
  METHODS
  GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured.
  
  
  RESULTS
  During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month.
  
  
  CONCLUSIONS
  The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation-induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Chan
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Williams
authors.forename: Patricia
authors.initials: P
authors.lastname: Raciti
authors.forename: Jennifer
authors.initials: J
authors.lastname: Blakeman
authors.forename: Theodore
authors.initials: T
authors.lastname: Kelesidis
authors.forename: Iosif
authors.initials: I
authors.lastname: Kelesidis
authors.forename: Michael L
authors.initials: ML
authors.lastname: Johnson
authors.forename: Michael O
authors.initials: MO
authors.lastname: Thorner
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D000328:Adult; D005215:Fasting / Q000097:blood*; D005260:Female; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D020738:Leptin / Q000172:deficiency* / Q000502:physiology* / Q000627:therapeutic use; D008297:Male
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D020738:Leptin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I