| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
1). During cell growth cycle of cultured rat hepatoma cells (dRLH-84) , cellular and nuclear uptake of triiodothyronine (T3) was manimal in early G1 phase, was gradually incresed toward late G1 phase. Levels of the nuclear T3 receptor also increased in late G1 phase. T3 promoted the proliferation of dRLH-84 cells through shortening of late G1 phase in this cell line. These data indicate that cells are sensitive to T3 in late G1 phase. On the other hand, cellular and nuclear thyroxine (T4) uptake was not altered during cell cycle, indicating the difference in the cellular transport mechanism between T3 and T4. Such a difference was also supported by the differences between T3 and T4 in increases of cellular and nuclear uptake after sodium butyrate treatment. 2) The thyromimetic compound, SK&F L-94901 (SKF) , exerts its activity on liver but not on heart or pituitary gland and may be useful for medical treatment of hyperlipidemia without extrahepatic adverse effects. We proved that SKF exerts liver-specific thyromimetic activity at the level of cellular transoprt of hormones, but not at the level of nuclear receptor. This suggests that cellular transport of thyroid hormone deffers among organs. 3). Recent studies suggest the involvement of cytokines (IL-1 beta, IL-6, TNF alpha) in pathogenesis of sick euthyroid syndrome (SES) . We found that alteration of thyroid hormone uptake and hormone action by cytokines, may explain decrese in basal and TRH-induced serum TSH levels despite low serum T3 levels in SES.The data also suggest that cytokines modify thyroid hormone action. 4) By means of Xenopus oocyte expression system, we proved that mRNA encoding cellular transporter of thyroid hormone exists in cultured rat pituitary cells (GH3 cells).
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