Ashizawa K, Cheng S Y
Gene Regulation Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9277-81. doi: 10.1073/pnas.89.19.9277.
Thyroid hormone receptors (TRs) are members of the steroid hormone/retinoic acid receptor superfamily, which regulate homeostasis, development, and differentiation. Their transcriptional activity is modulated by the thyroid hormone 3,3',5-triiodo-L-thyronine (T3). The present study evaluated the effect of the availability of cytoplasmic T3 on the modulation of transcriptional responses of the TRs. In human choriocarcinoma JEG-3 and monkey COS-1 cells, the cytosolic thyroid hormone binding protein is a monomer of the tetrameric pyruvate kinase, subtype M2, which does not bind T3. The in vivo monomer-tetramer interconversion is regulated by glucose via fructose 1,6-bisphosphate. At the physiological T3 concentration, lowering the glucose concentration led to an increase in the cellular concentration of the cytosolic thyroid hormone binding protein. By using a transient transfection system, a concomitant reduction in the transcriptional activity of the human beta 1 thyroid hormone receptor was detected in both cell lines. In the absence of glucose, the transcriptional activity of the human beta 1 thyroid hormone receptor in JEG-3 and COS-1 cells was reduced by 65-75% and 90-95%, respectively. However, glucose had no effect on the basal transcriptional activity. These findings demonstrate an important prenuclear step in the modulation of the gene regulating activity of the TRs.
甲状腺激素受体（TRs）是类固醇激素/视黄酸受体超家族的成员，该家族调节体内平衡、发育和分化。它们的转录活性受甲状腺激素3,3',5-三碘-L-甲状腺原氨酸（T3）的调节。本研究评估了细胞质T3的可用性对TRs转录反应调节的影响。在人绒毛膜癌JEG-3细胞和猴COS-1细胞中，胞质甲状腺激素结合蛋白是四聚体丙酮酸激酶M2亚型的单体，它不结合T3。体内单体-四聚体的相互转化由葡萄糖通过1,6-二磷酸果糖调节。在生理T3浓度下，降低葡萄糖浓度会导致胞质甲状腺激素结合蛋白的细胞浓度增加。通过使用瞬时转染系统，在两种细胞系中均检测到人类β1甲状腺激素受体的转录活性同时降低。在无葡萄糖的情况下，JEG-3细胞和COS-1细胞中人类β1甲状腺激素受体的转录活性分别降低了65%-75%和90%-95%。然而，葡萄糖对基础转录活性没有影响。这些发现证明了在调节TRs基因调控活性过程中一个重要的核前步骤。
