Regulation of two c-erbA messenger ribonucleic acids in rat GH3 cells by thyroid hormone.

Regulation of two c-erbA messenger ribonucleic acids in rat GH3 cells by thyroid hormone.
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甲状腺激素对大鼠 GH3 细胞中两种 c-erbA 信使核糖核酸的调节。

DOI:
10.1210/mend-2-6-479
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发表时间:
1988
影响因子:
--
通讯作者:
W. W. Chin
W. W. Chin
中科院分区:
医学2区
文献类型:
--
作者:
Mitchell A. Lazar;W. W. Chin

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近期有证据表明,c - erbA是甲状腺激素核受体,并且可能存在多个c - erbA基因。我们研究了三碘甲状腺原氨酸(T3)对生长激素3(GH3)细胞中两种c - erbA信使核糖核酸(mRNAs)的影响。从大鼠GH3细胞中分离出一种部分互补脱氧核糖核酸(cDNA),它与大鼠c - erbAα几乎完全相同(99.6%的核苷酸一致性),只是在对应于预测蛋白质序列羧基末端区域有一个独特的3'区域。这种cDNA(c - erbAα - 2)与大鼠c - erbAα一样,能与一种2.6千碱基(kb)的mRNA杂交,该mRNA不同于能与c - erbAβ杂交的6.2 kb的种类。由于核T3结合会被T3下调,我们假设一种或两种c - erbA mRNAs可能受T3调节。用10 nM的T3处理GH3细胞长达24小时,已知这种处理会使生长激素(GH)细胞中的核T3结合降低约2倍。在24小时时,6.2 kb和2.6 kb的mRNA种类都降低到接近对照值的50%。这些数据表明这两种c - erbA mRNAs受T3调节,并提示T3对GH细胞中T3结合活性的影响可能部分是通过下调c - erbA mRNA水平来介导的。
There is recent evidence suggesting that c-erbA is the thyroid hormone nuclear receptor, and that there may be multiple c-erbA genes. We investigated the effect of T3 on two c-erbA mRNAs present in GH3 cells. A partial cDNA was isolated from rat GH3 cells which is nearly identical (99.6% nucleotide identity) to rat c-erbA alpha, except for a unique 3'-region corresponding to the carboxyl terminal region of the predicted protein sequence. This cDNA (c-erbA alpha-2), like rat c-erbA alpha, hybridizes to a 2.6 kilobase (kb) mRNA which is distinct from a 6.2 kb species that hybridizes to c-erbA beta. Since nuclear T3-binding is down-regulated by T3, we hypothesized that one or both c-erbA mRNAs might be regulated by T3. GH3 cells were treated with 10 nM T3 for up to 24 h, a manipulation known to decrease nuclear T3 binding by approximately 2-fold in GH cells. Both the 6.2 kb and 2.6 kb mRNA species decreased to nearly 50% of control values at 24 h. These data indicate that these two c-erbA mRNAs are regulated by T3 and suggest that the T3 effect on T3 binding-activity in GH cells may be mediated, in part, by down-regulation of c-erbA mRNA levels.
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