The role of the IGF axis in IGFBP-1 and IGF-I induced renal enlargement in Snell dwarf mice
Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is generally believed to inhibit IGF action in the circulation. In contrast, IGFBP-1 has been reported to interact with cell surfaces and enhance IGF-I action locally in some tissues. Renal IGFBP-1 levels are found elevated in various conditions characterized by renal growth (e.g. diabetes mellitus, hypokalemia). To test whether IGFBP-1 is a renotropic factor, IGFBP-1 was administered alone or in combination with IGF-I to Snell dwarf mice, an in vivo model without compensatory feedback effects on growth hormone (GH) secretion. In three control groups of Snell dwarf mice, placebo, GH or IGF-I was administered. Compared with placebo, kidney weight increased in all treated groups, however, with different effects on kidney morphology. Administration of IGF-I, alone or in combination with IGFBP-1, tended to increase glomerular volume, while no changes were seen in the other groups. Administration of IGFBP-1 or IGFBP-1+IGF-I both caused dilatation of the thin limbs of Henle's loop, while GH or IGF-I administration had no visible effect. Furthermore, IGF-I administration resulted in an increased mean number of nuclei per cortical area and renal weight, whereas GH, IGF-I+IGFBP-1 or IGFBP-1 caused a decreased renal nuclei number. In situ hybridization and immunohistochemistry showed specific changes of the renal IGF system expression patterns in the different groups. Particularly, IGFBP-1 administration resulted in extensive changes in the mRNA expression of the renal IGF system, whereas the other administration regimen resulted in less prominent modifications. In contrast, administration of IGFBP-1 and IGFBP-1+IGF-I resulted in identical changes in the protein expression of the renal IGF system. Our results indicate that IGFBP-1, alone or in combination with IGF-I, demonstrated effects on the renal tubular system that differ from the effects of IGF-I.
|Keywords||Animals, Cell Count, Comparative Study, Female, Growth Disorders/*metabolism/pathology, Growth Hormone/*deficiency/pharmacology, Immunohistochemistry/methods, In Situ Hybridization/methods, Insulin-Like Growth Factor Binding Protein 1/*pharmacology, Insulin-Like Growth Factor I/analysis/genetics/*pharmacology, Kidney Glomerulus/drug effects/pathology, Kidney/*metabolism/pathology, Loop of Henle/drug effects/pathology, Male, Mice, Mice, Mutant Strains, Organ Size/drug effects, RNA, Messenger/analysis, Research Support, Non-U.S. Gov't|
van Kleffens, M., Lindenbergh-Kortleve, D.J., Koster, J.G., van Neck, J.W., Flyvbjerg, A., Rasch, R., … van Buul-Offers, S.C.. (2001). The role of the IGF axis in IGFBP-1 and IGF-I induced renal enlargement in Snell dwarf mice. Journal of Endocrinology. Retrieved from http://hdl.handle.net/1765/9695