Grant-in-Aid for international Scientific Research
|Allocation Type||Single-year Grants|
|Research Institution||The University of Tokyo|
NOGUCHI Tadashi The University of Tokyo, Faculty of Agriculture, Professor, 農学部, 教授 (50011937)
TAKAHASHI Shin-ichiro The University of Tokyo, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (00197146)
CONTI Marco Stanford University, School of Medicine, Associate Professor, 医学部, 助教授
VAN Wyk Juds ノースキャロライナ大学, 医学部, 教授
CLEMMONS Dav ノースキャロライナ大学, 医学部, 教授
UNDERWOOD Louis e. The University of North Carolina, School of Medicine, Professor, 医学部, 教授
VANWYK Judson j. The University of North Carolina, School of Medicine, Professor
CLEMMONS David r. The University of North Carolina, School of Medicine, Professor
|Project Period (FY)
1993 – 1994
Completed(Fiscal Year 1994)
|Budget Amount *help
¥7,000,000 (Direct Cost : ¥7,000,000)
Fiscal Year 1994 : ¥3,500,000 (Direct Cost : ¥3,500,000)
Fiscal Year 1993 : ¥3,500,000 (Direct Cost : ¥3,500,000)
|Keywords||Insulin-like growth factors / Insulin-like growth factor binding proteins / Insulin-like growth factor-I receptor / Tyrosine phosphorylation / Protein nutrition / Protein metabolism|
1) Plasma concentrations and gene expression of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) under various physiological conditions of rats : Using antibodies and cDNAs of these proteins, we measured the plasma concentrations and the amounts of tissues'mRNAs of IGF-I and IGFBPs under various physiological conditions. As a result, under protein malnutrition and diabetes, the concentrations of IGF-I,IGFBP-3 and IGFBP-4 decreased, however, the concentrations of IGFBP-1 and IGFBP-2 increased. Furthermore, the amounts of liver IGFBP-1 and IGFBP-2 mRNAs increased in response to protein restriction.
2) Regulation of transcription of rat IGF-I and IGFBP-1 genes : We have cloned 5'upstream regions oa rat IGF-I and IGFBP-1 genes. Especially, in the case of the IGFBP-1 gene, the different interaction of one fragment of 5'upstream region and liver nuclear extract prepared from control or protein-restricted rats, was observed.
3) Regulation of IGF-I an
d IGFBPs production in primary cultured liver parenchymal and nonparenchymal cells of rats : In liver parenchymal cells, growth hormone and insulin induced IGF-I production, and each hormone regulated IGFBP-1 and IGFBP-4 production in different manners. On the other hand, the IGFBP-3 production exclusively observed in nonparenchymal cells, furthermore, IGF-I stimulated its production. These results demonstrates the interrelationship between parenchymal and nonparenchymal cells in the production of IGF-I and IGFBPs in liver.
4) Interaction between cAMP-dependent and IGF-I dependent signal pathways in tyrosine phosphorylation in IGF-I-target cells : We found that pretreatment of FRTL-5 rat thyroid cells with TSH markedly potentiated the mitogenic response of IGF-I and the synergism between TSH and IGF-I was correlated with changes in tyrosine phosphorylation of intracellular proteins. In the process of priming cells to IGF-I by TSH treatment, cAMP-dependent tyrosine kinases may play important roles. Purification of important substrates of these tyrosine kinases is progressing. Less