Circulating IGF bioactivity is reduced under a variety of conditions where anabolism is impaired. Serum IGF binding activity is increased in acutely diabetic animals and is regulated according to
insulin status. Alterations in serum IGF binding activity reflects, at least in part, changes in circulating levels of
IGFBP-1, suggesting that
IGFBP-1 is an important modulator of IGF availability in post-natal life. Serum IGF binding activity and levels of
IGFBP-1 also are high in the hypoinsulinemic SGA fetal rat and levels of
IGFBP-1 correlate with fetal liver and
body weight, indicating that
IGFBP-1 contributes to the regulation of somatic growth in utero. Hepatic expression of
IGFBP-1 is regulated at the level of gene transcription by
insulin in a dominant negative fashion, while
glucocorticoids and cAMP analogues exert positive effects on hepatocellular
IGFBP-1 mRNA.
Glucocorticoids exert important effects on circulating levels and hepatic expression of
IGFBP-1 in vivo under conditions where
insulin levels are low. Regulation of hepatic production of
IGFBP-1 may provide a mechanism by which
insulin and counter-regulatory factors may modulate the availability of IGFs and the
biological effects of IGFs in both fetal and adult life.