Green N K, Franklyn J A, Ahlquist J A, Gammage M D, Sheppard M C
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston.
J Endocrinol. 1989 Jul;122(1):193-200. doi: 10.1677/joe.0.1220193.
The effect of tri-iodothyronine (T3) treatment on myocardial levels of alpha and beta myosin heavy chain (MHC) mRNAs in the rat was defined in vivo and in vitro. Dose-response experiments were performed in intact hypothyroid and euthyroid rats; in addition, studies in vitro examined the effect of T3 on MHC mRNAs in neonatal cardiac myocytes in primary culture. Specific alpha and beta MHC mRNAs were determined by Northern blot and dot hybridization to oligonucleotide probes complementary to the 3' untranslated regions of the MHC genes. An increase in myocardial beta MHC mRNA was demonstrated in hypothyroidism, accompanied by a reduction in alpha MHC mRNA. Marked differences in the sensitivity of alpha and beta MHC mRNAs to T3 replacement were found; a dose-dependent increase in alpha mRNA was evident at 6 h after T3 treatment, in the absence of consistent effects on beta mRNA, whereas 72 h after T3 replacement was commenced, stimulatory effects of T3 on alpha MHC mRNA, evident at all doses, were accompanied by a dose-dependent inhibition of beta MHC mRNA. No effect of thyroid status on actin mRNA was found, indicating the specificity of MHC gene regulation. T3 treatment of cardiac myocytes in vitro exerted similar actions on MHC mRNAs to those found in vivo, with a more marked influence on alpha than beta MHC mRNA. These studies of the action of T3 in vivo and in vitro have thus demonstrated specific effects of T3 on pretranslational regulation of the alpha and beta MHC genes, influences which differ not only in terms of stimulation or inhibition, but also in magnitude of effect.
在体内和体外研究了三碘甲状腺原氨酸（T3）治疗对大鼠心肌α和β肌球蛋白重链（MHC）mRNA水平的影响。在完整的甲状腺功能减退和甲状腺功能正常的大鼠中进行了剂量反应实验；此外，体外研究检测了T3对原代培养的新生心肌细胞中MHC mRNA的影响。通过Northern印迹和与MHC基因3'非翻译区互补的寡核苷酸探针的点杂交来测定特异性α和β MHC mRNA。甲状腺功能减退时心肌β MHC mRNA增加，同时α MHC mRNA减少。发现α和β MHC mRNA对T3替代的敏感性存在明显差异；T3治疗6小时后，α mRNA呈剂量依赖性增加，而对β mRNA无一致影响，而在开始T3替代72小时后，T3对α MHC mRNA的刺激作用在所有剂量下均明显，同时伴有β MHC mRNA的剂量依赖性抑制。未发现甲状腺状态对肌动蛋白mRNA有影响，表明MHC基因调控具有特异性。体外T3处理心肌细胞对MHC mRNA的作用与体内相似，对α MHC mRNA的影响比对β MHC mRNA更明显。因此，这些体内和体外T3作用的研究证明了T3对α和β MHC基因翻译前调控的特异性作用，这些影响不仅在刺激或抑制方面不同，而且在作用程度上也不同。
