Regulation of insulin-like growth factor (igf)-i and igf-binding
proteins by tumor necrosis factor.
Fan, Jie, Daniel Char, Gregory J. Bagby, Marie C. Gelato, Charles H.
Lang.
Department of Surgery/Division of Surgical Research and Department
of Medicine/Division of Endocrinology State University of New York at
Stony Brook, Stony Brook, NY and Department of Physiology, Louisiana
State University Medical Center, New Orleans, LA
APStracts 2:0171R, 1995.
The purpose of the present study was to determine 1) whether exogenous
administration of TNF[alpha] alters insulin-like growth factor (IGF)
-I and IGF binding proteins (BPs), and 2) whether the enhanced
endogenous production of TNF mediates the lipopolysaccharide (LPS)
-induced changes in the IGF system. The overnight infusion of murine
TNF[alpha] reduced circulating concentrations of both growth hormone
(GH) and IGF-I in fasted rats. Furthermore, TNF[alpha] decreased IGF
-I content in liver, gastrocnemius muscle and pituitary. In contrast,
TNF[alpha] increased IGF-I content in kidney and brain. IGFBP-1 was
increased in plasma, liver and muscle in response to TNF[alpha]. In a
second study, rats were injected with LPS after treatment with a
neutralizing anti-TNF antibody (Ab), and blood and tissues collected
4 h later. In LPS-treated rats, plasma concentrations of GH and IGF-I
were reduced. LPS also decreased the IGF-I content in liver and
skeletal muscle, and increased plasma, liver and muscle
concentrations of IGFBP-1. Pretreatment with anti-TNF Ab attenuated
the LPS-induced reduction in IGF-I and the increased IGFBP-1 in
plasma and liver, and completely prevented the decrease in IGF-I
observed in muscle. In contrast, the LPS-induced decrease in plasma
GH and the increased IGFBP-1 observed in muscle were unaltered by the
anti-TNF Ab. These results indicate that the GH/IGF axis is sensitive
to TNF[alpha] and that enhanced endogenous production of TNF mediates
a major portion of the LPS-induced decrease in IGF-I in plasma, liver
and muscle, as well as a smaller portion of the concomitant elevation
in IGFBP-1 in plasma and liver.
Received 10 February 1995; accepted in final form 13 June 1995.
APS Manuscript Number R103-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.