| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
To understand the mechanism of insulin-like growth factor-1 (IGF-1), as a secondary hormone of growth hormone, on brain development, we examined the central nervous system of the hormone-deficient Snell pituitary dwarf (dw), Little (lit), hypothyroid (hyt), congenital goiter (cog), and Pygmy (pg) mutant mice, which were showed hypomyelination in the cerebrum at the 40th day of age. Our findings are as follows : (1) there were no differences of IGF-1 concentration in the three parts of brain (cerebrum, brain stem, and cerebellum) between the 5 mutants and the normal control mice. Serum IGF-1 levels and IGF-1 concentraitons of liver and kidney in the dw, lit, hyt and cog mutant mice were found to be significantly lower than in the controls. These differences in IGF-1 concentration were not observed in the pg mouse. These results indicated that serum IGF-1 production is induced by thyroid hormones as well as by GH.(2) The serum IGF binding protein (IGFBP) -3 and IGFBP-4 levels were signif
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icantly reduced in dw, lit, hyt and cog mutant mice. IGFBP-2 levels were also reduced in the lit, hyt and cog mice, although that of the dw serum was found to be greatly elevated. No differences in the serum IGFBPs were found in the pg mouse. Consequently, the ration of IGFBP-3% : IGFBP-2% (the percentage of IGFBP-3 fraction of total IGFBP (IGFBP-3%) divided by that of IGFBP-2 (IGFBP-2%)) was decreased in GH-deficient mice but increased in hypothyroid mice, suggesting that IGFBP-3 and IGFBP-2 production in the liver is induced by GH and thyroid hormones respectively. (3) Serum IGF-1 level in the 20 day-old pg mouse was found to significantly decrease to 61% of the normal control. The liver and kidney IGF-1 levels in the 20 day-old pg mouse were also found to be lower than in the normal controls, 69% and 76% of the normal controls, respectively. The cerebrum and brain stem IGF-1 levels in the 20 day-old pg mouse were also found to be lower than in the normal controls, 89% and 65% of the normal controls, respectively. But no differences in IGF-1 level were found in the 20 day-old pg mouse cerebellum. These findings suggest that IGF-1 might have an indispensable role on neural development during the first 20 days of postnatal life. (4) There were no differences on both affinity cross-linking ^<125>I-labeled IGF-1 to microsomes prepared from the three parts of brain and phosphorylations of the beta subunits of the IGF-1 receptora in the three parts of brain between 40 day-old pg mouse and the normal control mouse. These results indicated that the pg mouse might have abnormalities on syntheses of IGF-1, IGFBPs and IGF-1 receptors at the prenatal and neonatal stage, and/or interactions between them on brain. Less
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