| Research Abstract |
Insulin-like growth factors (IGFs) bind to specific binding proteins (IGFBPs), and it has been speculated that the IGFBPs might modulate IGF action. In this study, we have investigated pathological significance of IGFBPs as follows. 1) Pathophysiological roles of IGFBP-6 have not been elucidated. Recently we measured serum IGFBP-6 by Western immunoblot (WIB), and have found that serum IGFBP-6 levels are not GH dependent and increase in patients with chronic renal failure (CRF). In the present study, to investigate further clinical significance and regulation of serum IGFBP-6, we measured serum IGFBP-6 levels in patients with CRF after renal transplantation. Furthermore, we also measured IGFBP-2 levels. Serum IGFBP-2 and -6 levels remarkably increased in all patients with CRF.The levels did not change after hemodialysis. Serum IGFBP-6 levels dramatically decreased 1 day after renal transplantation and decreased further with the improvement of renal function. In contrast to IGFBP-6, seru
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m IGFBP-2 levels did not decrease during 14 days after renal transplantation. In addition, we demonstrated IGFBP-6 in urine. These data indicate that IGFBP-6 might be excreted by the kidneys and serum IGFBP-6 levels might be related with renal function, and that regulation of serum IGFBP-6 levels are different from that of IGFBP-2.2) Serum levels of IGFBP-2 and IGFBP-3 in cord sera were higher and lower than those in adult sera. Serum levels of IGFBP-2 in cord sera inversely correlated with birth weight and the levels of free from of IGFs. The birth weight positively correlated with serum IGF-I,and free form of IGFs. These findings suggest that changes in IGFBP-2 in fetal sera might modulate the relative concentrations of free IGFs, supposed to be active from of IGFs, and then modulate fetal growth. 3) It has been hypothesized that IGFBP-1 play a role in counter regulation of blood glucose. We found that serum IGFBP-1 did not increase in 3h after insulin-induced hypoglycemia. Therefore, we could not support the hypothesis. 4) It has been reported that IGFBPs were regulated by various agents in osteoblast-like cells, but these data were different among species. In the present study, we took advantage of cultured human osteoblasts obtained from trabecular bone, and undertook a study of effect of various agents. The cultured human osteoblasts secreted IGFBPs, mainly IGFBP-3, -4, and -2.1,25-(OH)_2D_3 inhibited the proliferation of osteoblasts, and increased osteocalcin in the media. 1,25-(OH)_2D_3 increased IGFBP-3 and slightly IGFBP-4. E_2 did not affect on the cell proliferation and osteocalcin in the media, but, increased IGFBP-3, -4 and -2. These data demonstrate that IGFBPs of human osteoblasts are regulated by effectors of bone metabolism. However, it remains to be elucidated how IGFBPs modulate IGF action in bone metabolism. Less
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