DIFFERENTIAL EXPRESSION OF IGF-I AND IGF-BINDING PROTEIN-1 AND PROTEIN-2 IN PERIPORTAL AND PERIVENOUS ZONES OF RAT-LIVER

IGF-I has important roles in regulating growth and metabolism. Circula ting IGF-I is bound to specific binding proteins (IGFBP-1 to -6), with hepatocytes containing IGF-I, IGFBP-1 and -2 mRNA. Although many hepa tic proteins are regionally expressed in the liver acinus, no studies have reported zonation of IGF protein expression. In this study we inv estigated the pattern of hepatic mRNA for the IGF proteins, vs the pre viously reported periportal gradient of phosphoenolpyruvate carboxykin ase (PEPCK) expression. In situ hybridisation was used to analyse IGF- I, IGFBP-1, -2 and PEPCK mRNA in female Sprague-Dawley rats fed diets containing low (6%), normal (21%) or high (35%) protein. We report for the first time that IGFBP-1 and -2 and IGF-I are differentially expre ssed in the Liver acinus. In the normal- and high-protein groups, leve ls of IGFBP-1 mRNA were higher in the perivenous region, i.e. the oppo site gradient to PEPCK, with a higher gradient of IGFBP-1 expression i n the high-protein group. In contrast, IGFBP-2 had a similar pattern t o PEPCK, and a periportal gradient of IGF-I mRNA was also seen in the low-protein group. Using computerised image analysis, levels of IGFBP- 1 and -2 mRNA were elevated 2- and 10-fold respectively, in the low-vs normal-protein groups. The level of IGF-I mRNA was reduced to 65% of normal, with circulating IGF-I levels at 30% and insulin levels 39% of normal. These results demonstrate that hepatocytes are a heterogeneou s population with respect to regulation of IGF proteins, having specif ic expression patterns dependent on the position oi the hepatocyte wit hin the liver acinus.