| Co-Investigator(Kenkyū-buntansha) |
BOYAGES Stev ウエストメッド病院, 内分泌学研究室, 研究室長
CONTI Marco Stanfrod University, School of Medicine, Associate Professor, 医学部, 助教授
BAXTER Robert C. Baxter Kolling Institute of Medical Research, Professor, 教授
CLEMMONS Dav ノースキャロライナ大学, 医学部, 教授
VAN Wyk Juds ノースキャロライナ大学, 医学部, 教授
WYK Judson J.Van The University of North Carolina, School of Medicine, Professor
CLEMMONS David R. The University of North Carolina, School of Medicine, Professor
BOYAGES Steven C. Westmead Hospital, Department of Endocrinlogy, Department Chief
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| Research Abstract |
Recent evidence, derived from studies using knock-out or overexpression mice, indicates that insulinlike growth factors (IGFs) and/or their receptors are essential for the normal development and growth of mammals. Further, in many cell types IGFs have been shown to possess a variety of bioactivities, including the ability to induce cell proliferation and differentiaton, to inhibit cell apoptosis, and to maintain cell functio. IGFs circulates in the plasma and throughout the extracellular space as a complex with several specific binding proteins (IGFBPs). IGFBPs are believed at present to control half-lives of IGFs and modulate IGFs availability ; however, their physiological roles are still unclear. Despite the profuseness and diversity of IGFs bioactivities, the in vitro biological effects of IGFs are relatively weak and often are not demonstrable except in the presence of other hormones or growth factors. From this background, this study was undertaken to determine extracellular and
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intracellular mechanisms to modulate IGFs bioactivities in response to other hormones or growth factors, and different physiological conditions. Firstly, under various physiological conditions, we analyzed production of IGFs and IGFBPs interaction between IGFs and IGFBPs in serum, expression of IGF receptors. Our results suggested that expression of IGF/IGFBP/IGF receptors is regulated in different manners, resulting in reasonable IGFs bioactivities in response to each physiological situation. In additions, in endocrine cells, we demonstrated that tropic hormones prime cells to respond to IGF-I through cross-talk mechanisms of the intracellular signals. In liver cells, the similar potentiation between insulin and camp was observed, suggesting that the cross-talk mechanisms are very important to control insulin-like activities in general. From a series of these data, we concluded that IGF bioactivities are modulated by the process of 1) IGFs production, 2) IGFBPs production, 3) interaction between IGFs and IGFBPs, 4) IGF receptor expression, and 5) IGF signal transduction, in response to other hormones or growth factors as well as physiological conditions. This modulation must be required for normal development and growth of mammals. Less
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