Insulin-like growth factor binding protein-1: identification, purification, and regulation in fetal and adult life.

Abstract

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.