Regulation of insulin-like growth factor (igf)-i mrna and peptide,
and igf-binding proteins by interleukin-1.
Fan, Jie, Margaret M. Wojnar, Matthew Theodorakis, Charles H. Lang.
Department of Surgery, Division of Surgical Research, State
University of New York at Stony Brook, Stony Brook, New York
APStracts 2:0287R, 1995.
The purpose of the present study was to determine whether interleukin
(IL)-1 would alter the insulin-like growth factor (IGF) system in
rats and whether this change was mediated by glucocorticoids. The
IGF-I concentration was decreased in plasma (32%), liver (35%),
skeletal muscle (40-50% depending on fiber type), pituitary (36%) and
brain (52%), and increased in kidney (73%) 6 h after IV injection of
IL-1[beta]. IL-1[beta] also decreased IGF-I mRNA levels in liver and
muscle, and increased expression in kidney. These changes were
associated with a >2.5-fold elevation in plasma corticosterone
levels. Pretreatment of rats with the glucocorticoid receptor
antagonist RU 486 prevented the IL-1[beta] induced decrease in plasma
and liver IGF-I concentration, and the reduction in hepatic IGF-I
mRNA expression. In contrast, RU 486 did not significantly attenuate
the fall in IGF-I content in skeletal muscle, heart, brain or
pituitary, or the increase in IGF-I observed in kidney after IL
-1[beta]. Furthermore, pretreatment with RU 486 did not completely
prevent the IL-1[beta] induced decrease in IGF-I mRNA in skeletal
muscle. The concentration of both IGF binding protein (BP)-1 and -2
was increased in plasma, liver and muscle in response to IL-1[beta],
and these changes were also not prevented by RU 486. These results
indicate that the inflammatory cytokine IL-1[beta] is capable of
influencing multiple components of the IGF system. Whereas the
enhanced endogenous production of glucocorticoids appears to mediate
the IL-1[beta] induced decrease in IGF-I synthesis in liver, the
changes in IGF-I content observed in other tissues and the increase
in IGFBP-1 and -2 appears to be largely glucocorticoid-independent.
Received 30 November 1994; accepted in final form 18 October
1995.
APS Manuscript Number R687-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 November 95