EFFECT OF FASTING ON INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND GROWTH-HORMONE RECEPTOR MESSENGER-RNA LEVELS AND IGF-I GENE-TRANSCRIPTION IN RAT-LIVER
EFFECT OF FASTING ON INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND GROWTH-HORMONE RECEPTOR MESSENGER-RNA LEVELS AND IGF-I GENE-TRANSCRIPTION IN RAT-LIVER
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DOI：
10.1210/mend-4-1-91
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发表时间：
1990-01-01
影响因子：
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通讯作者：
TAKEMOTO, CD
中科院分区：
文献类型：
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作者：
STRAUS, DS;TAKEMOTO, CD
先前的研究表明，在禁食或维持蛋白质缺乏饮食的年轻生长大鼠中，循环胰岛素样生长因子-I（IGF-I）的浓度下降。为了研究IGF-I水平受营养调节的分子机制，我们测定了6周龄雄性对照大鼠、禁食24、48或72 h大鼠以及禁食48或72 h然后再进食24 h大鼠的IGF-I mRNA水平。几种IGF-I mRNA种类（8.0，4.0，1.7和1.0脂肪酶）的丰度在禁食动物中下降，并在再喂养24小时后反弹，尽管没有达到初始对照水平。空腹24 h后，IGF-I mRNA的1-磷酸酶减少了43%，空腹48 h后减少了76%，空腹72 h后减少了82%。禁食大鼠肝脏GH受体mRNA表达也降低。这表明，GH受体下调，发生在禁食是伴随着，并可能至少部分由GH受体mRNA的下降。GH受体mRNA下降的幅度和动力学与IGF-I mRNA下降的幅度和动力学相似，表明这两种mRNA可能受类似机制的调节。肝脏β-淀粉样蛋白水平没有显著变化。肌动蛋白或血清白蛋白mRNA的表达，表明IGF-I和GH受体mRNA的调节是特异性的。此外，脑IGF-II、β-IGF-II、β-IGF-II、β-IGF-II和β-IGF-II的水平也是显著的。肌动蛋白和α-肌动蛋白，微管蛋白mRNA没有显著变化的禁食。为了进一步阐明肝脏IGF-I mRNA调节的分子机制，使用从对照大鼠、禁食72 h大鼠和禁食再喂养大鼠的肝脏中分离的细胞核进行核转录延伸测定。各组内IGF-I基因转录存在相当大的动物间差异。IGF-I基因转录的平均水平在禁食动物中低于进食对照组。然而，这种降低并不具有统计学显著性，并且降低的幅度不能解释总IGF-I mRNA降低79%。这些结果表明，IGF-I mRNA的调节至少部分在转录后水平。
Previous studies have indicated that the concentration of circulating insulin-like growth factor-I (IGF-I) declines in young growing rats that have been fasted or maintained on a protein-deficient diet. To investigate the molecular mechanism(s) by which IGF-I levels are regulated by nutrition, we measured the levels of IGF-I mRNA in 6-week-old male control rats fed ad libitum, rats fasted for 24, 48, or 72 h, and rats fasted for 48 or 72 h and then refed for 24 h. The abundance of several IGF-I mRNA species (8.0, 4.0, 1.7, and 1.0 kilobases) decreased in the fasting animals and rebounded after 24 h of refeeding, although not to the initial control levels. The 1 kilobase IGF-I mRNA species exhibited a 43% decrease after 24 h of fasting, a 76% decrease after 48 h of fasting, and an 82% decrease after 72 h of fasting. Hepatic GH receptor mRNA also decreased in fasting rats. This indicates that the GH receptor down-regulation that occurs in fasting is accompanied by and probably at least partly caused by a decline in GH receptor mRNA. The magnitude and kinetics of the decline in GH receptor mRNA were similar to the magnitude and kinetics of the decline IGF-I mRNA, suggesting that the two mRNAs may be regulated by a similar mechanism. There was no significant change in the levels of liver .beta.-actin or serum albumin mRNA under the same conditions, indicating that the regulation of IGF-I and GH receptor mRNA was specific. In addition, the levels of brain IGF-II, .beta.-actin, and .alpha.-tubulin mRNAs were not significantly changed by fasting. To further elucidate the molecular mechanism for regulation of hepatic IGF-I mRNA, nuclear transcription elongation assays were performed using nuclei isolated from the liver of control rats, rats fasted for 72 h, and fasted-refed rats. There was considerable animal-to-animal variability in IGF-I gene transcription within each group. The mean level of IGF-I gene transcription was lower in the fasting animals than in the fed controls. However, this decrease was not statistically significant, and the magnitude of the decrease did not account for the 79% decrease in total IGF-I mRNA. These results suggest that IGF-I mRNA is regulated at least partly at the posttranscriptional level.