Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states

被引:50
作者
Chan, Jean L. [1 ]
Williams, Catherine J. [1 ]
Raciti, Patricia [1 ]
Blakeman, Jennifer [1 ]
Kelesidis, Theodore [1 ]
Kelesidis, Iosif [1 ]
Johnson, Michael L. [2 ]
Thorner, Michael O. [2 ]
Mantzoros, Christos S. [1 ]
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol Diabet & Metab, Boston, MA 02215 USA
[2] Univ Virginia Hlth Syst, Div Endocrinol & Metab, Charlottesville, VA 22908 USA
关键词
D O I
10.1210/jc.2008-0056
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: 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. Design, Setting, Patients, and Intervention: 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 methionylhumanleptin (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. Main Outcome Measures: 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.
引用
收藏
页码:2819 / 2827
页数:9
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