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The Effect of Growth Hormone on the Insulin-Like Growth Factor System during Fasting

Medical Department M (Endocrinology and Diabetes) (H.N., J.O.L.J., N.M., J.S.C., A.F.), Aarhus Kommunehospital, and Medical Research Laboratories (J.F., N.M., H.O., A.F.), Institute of Experimental Clinical Research, Aarhus University, DK-8000 Aarhus, Denmark

Address all correspondence and requests for reprints to: Helene Nørrelund, M.D., Ph.D., Medical Department M, Aarhus Kommunehospital, DK-8000 Aarhus C, Denmark. E-mail: helenenorrelund{at}dadlnet.dk.

The present study investigates the possible stimulatory effect of endogenous GH on IGF and IGF-binding protein (IGFBP) levels during fasting. Eight normal subjects were examined on four occasions: 1) in the basal postabsorptive state; 2) after 40 h of fasting; 3) after 40 h of fasting with somatostatin suppression of GH; and 4) after 40 h of fasting with suppression of GH and exogenous GH replacement. The two somatostatin experiments were identical in terms of hormone replacement (except for GH). Short-term fasting led to a 50% reduction in free IGF-I. The reduction in free IGF-I was paralleled by an increase in IGFBP-1, an increase in the complex formation of IGFBP-1 and IGF-I, and a modest reduction in IGFBP-3 proteolysis. GH deprivation during fasting led to a 35% reduction in total IGF-I and a 70% reduction in free IGF-I. GH replacement increased free and total IGF-I to levels similar to those observed during plain fasting and decreased IGFBP-1, however, without affecting IGFBP-1-bound IGF-I. Finally, IGFBP-3 proteolysis was slightly increased by GH replacement. In conclusion, the major new finding of the present study is that the GH hypersecretion seen during short-term fasting is not merely secondary to a reduction in IGF bioactivity.

This work was supported by the Danish Research Council Grant 9600822 (Aarhus University–Novo Nordisk Centre for Research in Growth and Regeneration) and Grants 9700592 and 22020141; the Eva and Henry Frænkels Memorial Foundation; and the Hørslev Foundation.

Abbreviations: IGFBP, IGF-specific binding protein; IRMA, immunoradiometric assay; rh, recombinant human; tIGF, total IGF; WIB, Western immunoblotting; WLB, Western ligand blotting.

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