Human insulin-like growth factor (IGF) binding protein-1 inhibits IGF-I-stimulated body growth but stimulates growth of the kidney in Snell dwarf mice

The actions of insulin-like growth factor-I (IGF-I) are modulated by IGF bi nding proteins (IGFBPs). The effects of IGFBP-1 in vivo are insufficiently known, with respect to inhibitory or stimulatory actions on IGF-induced gro wth of specific organs. Therefore, we studied the effects of IGFBP-1 on IGF -I-induced somatic and organ growth in pituitary-deficient Snell dwarf mice . Human GH, IGF-I, IGFBP-1, and a preequilibrated combination of equimolar amounts of IGF-I and IGFBP-1 were administered sc during 4 weeks. Treatment with IGF-I alone induced a significant increase in body length (1 08% of control) and weight (112%) as well as an increase in weight of the s ubmandibular salivary glands (135%), kidneys (124%), femoral muscles (111%) , testes (129%), and spleen (126%) compared with saline-treated controls. I GFBP-1 alone induced a significant increase in weight of the kidneys (152% of control). Coadministration of IGF-I with IGFBP-1 neutralized the stimula ting effects of IGF-I on body length and weight as well as on the femoral m uscles and testes. in contrast, the weights of the submandibular salivary g lands (143%) were not significantly different from those of IGF-I-treated a nimals, whereas the weights of the kidneys (171%) and spleen (156%) were si gnificantly increased compared with IGF-I-treated mice. The effect of IGFBP -1 plus IGF-I on kidney weight was not significantly greater than the effec t of IGFBP-1 alone. Western ligand blotting showed induction of the IGFBP-3 doublet as well as IGFBPs with molecular masses of 24 kDa, most probably IGFBP-4, by human GH, IGF-I alone, and IGF-I in combination with IGFBP-1. Our data show that coadministration of IGFBP-1 inhibits IGF-I-induced body growth of GH-deficient mice but significantly stimulates the growth promoti ng effects of TGF-I on the kidneys and the spleen. These data warrant furth er investigation because differences in concentrations of IGFBP-1 occurring in vivo may influence IGF-I-induced anabolic processes.