Differential expression of IGF-I and IGF-binding protein-1 and -2 in periportal and perivenous zones of rat liver

• Published in: Journal of endocrinology Vol. 157; no. 2; pp. 285 - 294
• Main Authors: Hazel, SJ, Nordqvist, AC, Hall, K, Nilsson, M, Schalling, M
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01.05.1998; Portland Press
• Subjects: Animals; Autoradiography; Biological and medical sciences; Dietary Proteins - administration & dosage; Female; Fundamental and applied biological sciences. Psychology; Image Processing, Computer-Assisted; In Situ Hybridization; Insulin - blood; Insulin-Like Growth Factor Binding Protein 1 - genetics; Insulin-Like Growth Factor Binding Protein 1 - metabolism; Insulin-Like Growth Factor Binding Protein 2 - genetics; Insulin-Like Growth Factor Binding Protein 2 - metabolism; Insulin-Like Growth Factor I - analysis; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - metabolism; Liver - metabolism; Liver. Bile. Biliary tracts; Medicin och hälsovetenskap; Phosphoenolpyruvate Carboxykinase (ATP) - metabolism; Rats; Rats, Sprague-Dawley; RNA, Messenger - analysis; Vertebrates: digestive system; Rat; Digestive system; Enzyme; Liver; Rodentia; Lyases; Gene expression; Insulin like growth factor 1; Insulin like growth factor binding protein; Carbon-carbon lyases; Vertebrata; Mammalia; Carboxy-lyases; Localization; Phosphoenolpyruvate carboxykinase (ATP)
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.0.1570285

IGF-I has important roles in regulating growth and metabolism. Circulating IGF-I is bound to specific binding proteins (IGFBP-1 to -6), with hepatocytes containing IGF-I, IGFBP-1 and -2 mRNA. Although many hepatic proteins are regionally expressed in the liver acinus, no studies have reported zonation of IGF protein expression. In this study we investigated the pattern of hepatic mRNA for the IGF proteins, vs the previously reported pepriportal gradient of phosphoenolpyruvate carboxykinase (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 expressed in the liver acinus. In the normal- and high-protein groups, levels of IGFBP-1 mRNA were higher in the perivenous region, i.e. the opposite gradient to PEPCK, with a higher gradient of IGFBP-1 expression in the high-protein group. In contrast, IGFBP-2 had a similar pattern to 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 heterogeneous population with respect to regulation of IGF proteins, having specific expression patterns dependent on the position of the hepatocyte within the liver acinus.