Segal J, Ingbar S H
Endocrinology. 1984 Jul;115(1):160-6. doi: 10.1210/endo-115-1-160.
In previous studies we have shown that the thyroid hormone T3 induces a prompt increase in the cAMP concentration of rat thymocytes in vitro. This is followed by and very likely leads to an increase in cellular uptake of the glucose analog 2-deoxyglucose (2-DG). Since these effects of T3 were shown to require the presence of Ca2+ in the suspending medium, it seemed reasonable to determine whether T3 would influence the metabolism of calcium itself. In standard medium containing 1 mM Ca2+ and 45Ca as a tracer, T3 induced a very prompt, dose-related, but transient, increase in thymocyte calcium accumulation. This effect was evident within the first minute after the addition of T3 (including processing time) and is to our knowledge the most rapid effect of T3 yet demonstrated. The effect reached a maximum very shortly thereafter and then abated within a few minutes. Uptake of 45Ca from Ca2+-free medium (5 microM Ca2+ as a contaminant) was also increased by T3, but under these conditions, the increase was sustained for the entire 120-min period of study. At a concentration of 25 microM, lanthanum (La3+) unexpectedly produced a rapid and marked (4- to 6-fold) increase in 45Ca accumulation in the thymocytes. The increase in cellular calcium accumulation produced by La3+ was not associated with any effect on thymocyte cAMP concentration or 2-deoxyglucose (2-DG) uptake. However, La3+ potentiated the response of the cell to T3 in respect to calcium accumulation, cAMP concentration, and 2-DG uptake, shifting the dose-response curve of the latter two effects to the left. In view of the calcium dependence of the T3 effect on thymocyte cAMP concentration and 2-DG uptake, and the effect of La3+ to concomitantly enhance the sensitivity of the cell to the effects of T3 on calcium accumulation and cAMP and 2-DG metabolism, we suggest that the prompt increase in cellular Ca2+ uptake induced by T3 that we demonstrated is causally related to its subsequent effect on cellular cAMP concentration and 2-DG uptake.
在先前的研究中，我们已经表明甲状腺激素T3在体外可迅速提高大鼠胸腺细胞的cAMP浓度。随后，这很可能导致葡萄糖类似物2-脱氧葡萄糖（2-DG）的细胞摄取增加。由于已证明T3的这些作用需要悬浮培养基中存在Ca2+，因此确定T3是否会影响钙本身的代谢似乎是合理的。在含有1 mM Ca2+和作为示踪剂的45Ca的标准培养基中，T3可迅速诱导胸腺细胞钙积累呈剂量相关但短暂的增加。在添加T3后的第一分钟内（包括处理时间），这种效应就很明显，据我们所知，这是迄今为止所证明的T3最迅速的效应。此后不久，该效应达到最大值，然后在几分钟内减弱。T3也增加了从无Ca2+培养基（5 microM Ca2+作为污染物）中摄取45Ca的量，但在这些条件下，这种增加在整个120分钟的研究期间持续存在。在浓度为25 microM时，镧（La3+）意外地使胸腺细胞中45Ca的积累迅速且显著增加（4至6倍）。La3+引起的细胞钙积累增加与对胸腺细胞cAMP浓度或2-脱氧葡萄糖（2-DG）摄取没有任何影响。然而，就钙积累、cAMP浓度和2-DG摄取而言，La3+增强了细胞对T3的反应，使后两种效应的剂量反应曲线向左移动。鉴于T3对胸腺细胞cAMP浓度和2-DG摄取的效应依赖于钙，以及La3+同时增强细胞对T3对钙积累、cAMP和2-DG代谢效应的敏感性，我们认为我们所证明的T3诱导的细胞Ca2+摄取迅速增加与其随后对细胞cAMP浓度和2-DG摄取的效应存在因果关系。
