Saji M, Kohn L D
Section on Cell Regulation, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Endocrinology. 1990 Oct;127(4):1867-76. doi: 10.1210/endo-127-4-1867.
In FRTL-5 rat thyroid cells, hydrocortisone alters two TSH-increased cAMP-mediated activities in an opposite manner. Thus, in a concentration-dependent fashion, hydrocortisone synergistically enhances TSH-increased thymidine incorporation into DNA, whereas it inhibits TSH-induced iodide uptake. The effect of hydrocortisone on TSH-increased thymidine incorporation is specific, in that it has only a minimal ability by itself to increase thymidine incorporation into DNA and slightly inhibits the activity of insulin or insulin-like growth factor-I. The effect of hydrocortisone on TSH-induced iodide uptake does not result from altered iodide efflux, but, rather, from a decrease in the maximal velocity, not the Km, of iodide influx, i.e. from a decrease in the effective number of iodide porters. The action of a cAMP analog to increase thymidine incorporation into DNA or iodide uptake was also increased or decreased, respectively, by hydrocortisone, whereas hydrocortisone did not diminish the ability of TSH to increase cAMP levels in the cells. The different effect of hydrocortisone on these two cAMP-mediated activities reflects, therefore, regulation of cAMP signal action rather than the ability of TSH to generate a cAMP signal. Twenty-four hours after TSH, actinomycin-D superinduces iodide uptake and abolishes the action of hydrocortisone to inhibit iodide uptake. It has been suggested that actinomycin-D superinduces iodide uptake in FRTL-5 cells by a posttranscriptional action, inhibition of mRNA degradation, rather than by its known transcriptional actions linked to DNA synthesis. More recent studies of the effect of actinomycin-D, given under identical circumstances, on TSH-stimulated malic enzyme mRNA levels directly validate this hypothesis. We, thus, suggest that the opposite action of hydrocortisone on the two cAMP-mediated activities may reflect positive and negative regulation of the action of cAMP at different steps in the transduction process, one being transcriptional (DNA synthesis) and the other posttranscriptional (induction of iodide porter activity).
在FRTL-5大鼠甲状腺细胞中，氢化可的松以相反的方式改变两种促甲状腺激素（TSH）增加的环磷酸腺苷（cAMP）介导的活性。因此，氢化可的松以浓度依赖的方式协同增强TSH增加的胸苷掺入DNA的能力，而抑制TSH诱导的碘摄取。氢化可的松对TSH增加的胸苷掺入的作用是特异性的，因为它自身增加胸苷掺入DNA的能力极小，并且轻微抑制胰岛素或胰岛素样生长因子-I的活性。氢化可的松对TSH诱导的碘摄取的作用不是由于碘外流改变，而是由于碘内流的最大速度降低，而不是米氏常数（Km）降低，即碘转运体的有效数量减少。cAMP类似物增加胸苷掺入DNA或碘摄取的作用也分别被氢化可的松增强或减弱，而氢化可的松并未削弱TSH增加细胞内cAMP水平的能力。因此，氢化可的松对这两种cAMP介导的活性的不同作用反映了cAMP信号作用的调节，而不是TSH产生cAMP信号的能力。TSH作用24小时后，放线菌素-D超诱导碘摄取并消除氢化可的松抑制碘摄取的作用。有人提出，放线菌素-D通过转录后作用，即抑制mRNA降解，而不是通过其与DNA合成相关的已知转录作用，在FRTL-5细胞中超诱导碘摄取。最近在相同条件下对放线菌素-D对TSH刺激的苹果酸酶mRNA水平的影响进行的研究直接证实了这一假设。因此，我们认为氢化可的松对两种cAMP介导的活性的相反作用可能反映了cAMP在转导过程中不同步骤作用的正负调节，一个是转录水平（DNA合成），另一个是转录后水平（碘转运体活性诱导）。
