Guissouma H, Ghorbel M T, Seugnet I, Ouatas T, Demeneix B A
Laboratoire de Physiologie Générale et Comparée, Muséum National d'Histoire Naturelle, URA CNRS 90, 75231 Paris, Cedex 5, France.
FASEB J. 1998 Dec;12(15):1755-64. doi: 10.1096/fasebj.12.15.1755.
Thyroid hormone (tri-iodo-thyronine, T3) exerts transcriptional effects on target genes in responsive cells. These effects are determined by DNA/protein interactions governed by the type of T3 receptors (TRs) in the cell. As TRs show tissue and developmental variations, regulation is best addressed in an integrated in vivo model. We examined TR subtype effects on thyrotropin-releasing hormone (TRH) transcription and on the pituitary/thyroid axis end point: thyroid hormone secretion. Polyethylenimine served to transfect a TRH-luciferase construct containing 554 bp of the rat TRH promoter into the hypothalami of newborn mice. Transcription from the TRH promoter was regulated in a physiologically faithful manner, being significantly increased in hypothyroidism and decreased in T3-treated animals. Moreover, when various ligand binding forms of mouse or chicken TRbeta and TRalpha were expressed with TRH-luciferase, all forms of TRbeta gave T3-dependent regulation of TRH transcription, whereas transcription was T3 insensitive with each TRalpha tested. Moreover, chicken TRalpha increased TRH transcription sixfold, whereas mouse TRalpha decreased transcription. These transcriptional effects had correlated physiological consequences: expression of the chicken TRalpha in the hypothalamus of newborn mice raised circulating T4 levels by fourfold, whereas mouse TRalpha had opposite effects. Thus, TR subtypes have distinct, physiologically relevant effects on TRH transcription.
甲状腺激素（三碘甲状腺原氨酸，T3）对反应性细胞中的靶基因发挥转录作用。这些作用由细胞中T3受体（TRs）类型所支配的DNA/蛋白质相互作用决定。由于TRs表现出组织和发育上的差异，因此最好在一个整合的体内模型中研究其调控机制。我们研究了TR亚型对促甲状腺激素释放激素（TRH）转录以及垂体/甲状腺轴终点指标——甲状腺激素分泌的影响。聚乙烯亚胺用于将包含大鼠TRH启动子554 bp的TRH - 荧光素酶构建体转染到新生小鼠的下丘脑。TRH启动子的转录以生理上可靠的方式受到调控，在甲状腺功能减退时显著增加，而在T3处理的动物中则减少。此外，当小鼠或鸡的TRβ和TRα的各种配体结合形式与TRH - 荧光素酶一起表达时，所有形式的TRβ都对TRH转录产生T3依赖性调控，而所测试的每种TRα的转录对T3不敏感。此外，鸡的TRα使TRH转录增加了六倍，而小鼠的TRα则降低了转录。这些转录作用具有相关的生理后果：在新生小鼠下丘脑表达鸡的TRα使循环T4水平提高了四倍，而小鼠的TRα则产生相反的作用。因此，TR亚型对TRH转录具有不同的、与生理相关的作用。
