Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states.
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.
Chan
Jean L
JL
Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
Williams
Catherine J
CJ
Raciti
Patricia
P
Blakeman
Jennifer
J
Kelesidis
Theodore
T
Kelesidis
Iosif
I
Johnson
Michael L
ML
Thorner
Michael O
MO
Mantzoros
Christos S
CS
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
D018969:Insulin-Like Growth Factor Binding Proteins; D020738:Leptin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I