Differential regulation of transcription initiation from insulin-like growth factor-I (IGF-I) leader exons and of tissue IGF-I expression in response to changed growth hormone and nutritional status in sheep.
Differential regulation of transcription initiation from insulin-like growth factor-I (IGF-I) leader exons and of tissue IGF-I expression in response to changed growth hormone and nutritional status in sheep.
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胰岛素样生长因子-I (IGF-I) 前导外显子的转录起始和组织 IGF-I 表达的差异调节，以响应绵羊生长激素和营养状况的变化。
DOI：
10.1210/endo.132.4.8462477
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发表时间：
1993
期刊：
影响因子：
4.8
通讯作者：
R. Gilmour
中科院分区：
文献类型：
--
作者：
J. Pell;J. Saunders;R. Gilmour
在哺乳动物胰岛素样生长因子-I(IGF-I)基因中，外显子1和2被差异剪接到外显子3，产生交替的1类和2类转录本。本研究的目的是研究由于长期控制营养和生长激素状态而导致的不同生长速度的羔羊中这些先导外显子的组织表达。开发了核探针，以便可以使用单个核糖核酸酶保护试验来确定先导外显子特异性和总IGF-I基因的表达。羔羊随机或限量摄入蛋白质含量高或低的日粮；在这些日粮组中，他们接受生理盐水或生长激素治疗10周。在生长激素(P=0.004)、蛋白质(P=0.002)和能量(P<；0.001)状态下，肝脏总IGF-I转录本显著增加，循环IGF-I浓度(GH，P<；0.001；蛋白质，P=0.026；能量，P<；0.001)显著增加。外显子1和外显子2在肝脏中表达，但表达程度不同。膳食能量和蛋白质的增加导致了第一类和第二类转录产物的表达增加，但第二类基因的表达增加的百分比至少是第一类基因的5倍。GH处理只刺激2类转录本的表达显著增加。在低蛋白、能量受限、盐水处理的羔羊中，外显子1的转录本约占1类和2类转录本总数的70%，这一比例随着1类和2类转录本的显著下降而显著下降，并且在高蛋白、随意饲喂和生长激素处理的动物中，随着生长激素和营养状况的增加，这一比例显著下降；因此，2类转录本表现出相反的表达模式。这些数据表明，在正常生理范围内受到刺激的完整动物中，外显子2可能比外显子1敏感得多。肌肉中IGF-I基因的表达至少比肝脏低20倍，主要由1类转录本组成。肌肉总IGF-I mRNA对营养状态的改变或GH处理不敏感，即使在自由摄取和GH处理后肌肉生长显著增加，这表明肝脏来源的内分泌IGF-I可能在肌肉生长调节中起作用。
In the mammalian insulin-like growth factor-I (IGF-I) gene, exons 1 and 2 are differentially spliced to exon 3 producing alternate class 1 and class 2 transcripts. The aim of this study was to investigate the tissue expression of these leader exons in lambs growing at different rates as a result of chronic manipulation of nutritional and GH status. Riboprobes were developed so that leader exon-specific and total IGF-I gene expression could be determined using a single RNase protection assay. Lambs were fed a diet containing high or low protein content either ad libitum or at a restricted intake; within these dietary groups they were treated with either saline or GH for 10 weeks. Total hepatic IGF-I messenger RNA (mRNA) transcripts were significantly increased by GH (P = 0.004), protein (P = 0.002), and energy (P < 0.001) status as were circulating IGF-I concentrations (GH, P < 0.001; protein, P = 0.026; energy, P < 0.001). Exons 1 and 2 were expressed in liver but to a variable extent. Increased dietary energy and protein induced increased expression from both class 1 and 2 transcripts, but the percent increases was at least 5-fold greater for class 2 than for class 1 mRNA. GH treatment only stimulated significant increases in expression from class 2 transcripts. In the low protein, energy-restricted, saline-treated lambs exon 1 transcripts accounted for approximately 70% of total class 1 and 2 transcripts, and this proportion declined significantly as class 1 and 2 transcripts, and this proportion declined significantly as GH and nutritional status increased to only 30% in the high protein, ad libitum-fed, GH-treated animals; class 2 transcripts therefore displayed the opposite pattern of expression. These data indicate that exon 2 may be far more sensitive than exon 1 in intact animals which have been stimulated within normal physiological limits. Muscle IGF-I gene expression was at least 20-fold less than that for the liver and consisted mainly of class 1 transcripts. Muscle total IGF-I mRNA was insensitive to changed nutritional status or to GH treatment, even though significant increases in muscle growth occurred in response to ad libitum intake and GH, indicating that hepatically derived endocrine IGF-I could have a role in the regulation of muscle growth.
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DOI：
10.1677/joe.0.1300305
发表时间：
1991-08
期刊：
The Journal of endocrinology
影响因子：
--
作者：
M. VandeHaar;B. Moats-Staats;M. Davenport;J. Walker;J. Ketelslegers;B. Sharma;L. Underwood
通讯作者：
M. VandeHaar;B. Moats-Staats;M. Davenport;J. Walker;J. Ketelslegers;B. Sharma;L. Underwood
DOI：
10.1016/s0021-9258(18)92881-4
发表时间：
1991-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Y. Kajimoto;P. Rotwein
通讯作者：
Y. Kajimoto;P. Rotwein
在生长激素刺激的肌肉肥大过程中诱导 IGF-I 和 -II 的 mRNA。
DOI：
10.1152/ajpendo.1988.255.4.e513
发表时间：
1988
期刊：
The American journal of physiology
影响因子：
--
作者：
Turner,JD;Rotwein,P;Novakofski,J;Bechtel,PJ
通讯作者：
Bechtel,PJ
DOI：
10.1073/pnas.83.24.9343
发表时间：
1986-12-01
影响因子：
11.1
作者：
MATHEWS, LS;NORSTEDT, G;PALMITER, RD
通讯作者：
PALMITER, RD
大鼠胎儿和成人组织中的生长调节素-C/胰岛素样生长因子-I 和胰岛素样生长因子-II mRNA。
DOI：
--
发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lund,PK;Moats-Staats,BM;Hynes,MA;Simmons,JG;Jansen,M;D'Ercole,AJ;VanWyk,JJ
通讯作者：
VanWyk,JJ