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.
van Kleffens
M
M
Laboratory of Pediatrics, Subdivision of Molecular Endocrinology, Erasmus University Rotterdam, The Netherlands.
Lindenbergh-Kortleve
D J
DJ
Koster
J G
JG
van Neck
J W
JW
Flyvbjerg
A
A
Rasch
R
R
Drop
S L
SL
van Buul-Offers
S C
SC
D000818:Animals; D002452:Cell Count; D005260:Female; D006130:Growth Disorders / Q000378:metabolism* / Q000473:pathology; D013006:Growth Hormone / Q000172:deficiency* / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008138:Loop of Henle / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis
D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone