The role of the IGF axis in IGFBP-1 and IGF-1 induced renal enlargement inSnell dwarf mice

Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is generally b elieved to inhibit IGF action in the circulation. In contrast, IGFBP-1 has been reported to interact with cell surfaces and enhance IGF-I action local ly in some tissues. Renal IGFBP-1 levels are found elevated in various cond itions characterized by renal growth (e.g. diabetes mellitus. hypokalemia), To test whether IGFBP-1 is a renotropic factor. IGFBP-1 was administered al one or in combination with IGF-I to Snell dwarf mice, an fit vivo, model wi thout compensatory Feedback effects on growth hormone (GH) secretion, In th ree control groups of Snell dwarf mice. placebo, GH or IGF-I was administer ed. Compared with placebo. kidney weight increased in all treated groups, h owever, with different effects on kidney morphology. Administration of IGF- I. alone or in combination with IGFBP-1, tended to increase glomerular volu me, 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 loo p,, while GH or IGF-I administration had no visible effect. Furthermore, IG F-I administration resulted in an increased mean number of nuclei per corti cal area and renal weight, whereas GH, IGF-I+IGFBP-1 or IGFBP-1 caused a de creased renal nuclei number. In situ hybridization and immunohistochemistry showed ges of the renal IGF system expression specific cham pattern,, in the different groups. Particul arly, IGFBP-1 administration resulted in extensive changes in the mRNA expr ession of the renal IGF system, whereas the other administration regimen re sulted in less prominent modifications. In contrast, administration of IGFB P-1 and IGFBP-1+IGF-I resulted in identical changes in the protein expressi on of the renal IGF system. Our results indicate that IGFBP-1, alone or in combination with IGF-I, demo nstrated effects on the renal tubular system that differ front the effects of IGF-I.