Laverriere J N, Morin A, Tixier-Vidal A, Truong A T, Gourdji D, Martial J A
Laboratoire de Génie Génétique, Institut de Chimie B6, Université de Liège, Sart-Tilman, Belgium.
EMBO J. 1983;2(9):1493-9. doi: 10.1002/j.1460-2075.1983.tb01613.x.
The hypothalamic tripeptide thyroliberin (TRH) regulates prolactin (PRL) and growth hormone (GH) synthesis inversely by modulating the levels of their specific mRNA. Changes in mRNA levels could involve both transcriptional and posttranscriptional events. To examine further these possibilities, we have investigated the effect of TRH on the biosynthesis and degradation of PRL and GH RNA in a rat pituitary tumor cell line. Newly synthesized PRL and GH RNA sequences were quantified in nuclear and cytoplasmic fractions by hybridization of 3H-labelled RNA to immobilized plasmid DNA containing either PRL or GH cDNA sequences. Steady-state levels of specific RNA were estimated by RNA blot hybridization. The results indicate that TRH increases in a rapid but transient manner the transcription of the PRL gene, and suggest that it does not alter the processing and the transport to the cytoplasm. In contrast, after a lag-time, TRH seems to induce a long-lasting inhibition on GH, as well as on overall gene transcription. Furthermore, we observed an effect of TRH on mRNA stability. TRH significantly increases the half-life of PRL mRNA. Our results also support the hypothesis that TRH decreases the half-life of GH mRNA. Such post-transcriptional action of TRH amplifies and prolongs the regulations exerted at the transcriptional level.
下丘脑三肽促甲状腺激素释放激素（TRH）通过调节催乳素（PRL）和生长激素（GH）特异性mRNA的水平，以相反的方式调节它们的合成。mRNA水平的变化可能涉及转录和转录后事件。为了进一步研究这些可能性，我们研究了TRH对大鼠垂体肿瘤细胞系中PRL和GH RNA生物合成及降解的影响。通过将3H标记的RNA与含有PRL或GH cDNA序列的固定化质粒DNA杂交，对核和细胞质部分中新合成的PRL和GH RNA序列进行定量。通过RNA印迹杂交估计特异性RNA的稳态水平。结果表明，TRH以快速但短暂的方式增加PRL基因的转录，并且表明它不会改变加工过程和向细胞质的转运。相反，经过一段延迟时间后，TRH似乎对GH以及整体基因转录产生持久的抑制作用。此外，我们观察到TRH对mRNA稳定性有影响。TRH显著增加PRL mRNA的半衰期。我们的结果也支持TRH降低GH mRNA半衰期的假设。TRH的这种转录后作用放大并延长了在转录水平上施加的调节。
