Tahara K, Saji M, Aloj S M, Kohn L D
Section on Cell Regulation, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Adv Exp Med Biol. 1989;261:295-326. doi: 10.1007/978-1-4757-2058-7_12.
The present study and the previous report (6) show that the cyclooxygenase path is a primary route of metabolism of arachidonic acid in FRTL-5 rat thyroid cells. The production of PGD2 and PGE2 is an active process in intact cells treated with complete medium including TSH, insulin and 5% calf serum. In contrast, PGF2 alpha and HHT are probably nonenzymatic degradation products of an unstable intermediate, PGH2, since the two compounds are produced and occupy a significant proportion of the cyclooxygenase metabolites only in the homogenate system; this is true in other cells. Although the production of prostaglandins involves three steps, i.e. the release of free arachidonic acid, the production of PGH2 by PGH synthase (cyclooxygenase) and the conversion of PGH2 to various prostaglandins by specific isomerases or synthetases, the first step, the release of free arachidonic acid, has been, until recently, believed to be the sole step important for the regulation of prostaglandin synthesis. This presumption rested on the following observations. Only the free form of arachidonic acid is converted to prostaglandins and the intracellular free arachidonic acid pool is very small compared to the esterified form in phospholipids. The size of the free arachidonic acid pool is regulated by the balance between release from phospholipids by phospholipases and reacylation into phospholipids. When resting cells are stimulated, the release of arachidonic acid and the production of prostaglandins increase concomitantly. The present study shows, however, that all three steps of prostaglandin synthesis are under regulatory control in FRTL-5 rat thyroid cells and that the control is a complex process involving TSH, insulin/IGF-I, and serum. The first step is primarily under the control of TSH. TSH increases the synthesis of arachidonic acid and also, like norepinephrine (5, 6) induces the release of arachidonic acid from the cell by a mechanism involving a pertussis toxin-sensitive G protein. Regulation of the second step can be estimated by measuring cyclooxygenase activity. The present report shows that TSH increases cyclooxygenase activity, presumably by increasing gene expression, but that the TSH effect on cyclooxygenase activity requires insulin/IGF-I or serum. This result is similar to studies showing the effect of TSH and insulin/IGF-I on glycosaminoglycan synthesis, thyroglobulin synthesis, and growth in FRTL-5 thyroid cells.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究及之前的报告（6）表明，环氧化酶途径是FRTL-5大鼠甲状腺细胞中花生四烯酸代谢的主要途径。在含有促甲状腺激素（TSH）、胰岛素和5%小牛血清的完全培养基处理的完整细胞中，前列腺素D2（PGD2）和前列腺素E2（PGE2）的产生是一个活跃的过程。相比之下，前列腺素F2α（PGF2α）和12-羟基-5,8,10,14-二十碳四烯酸（HHT）可能是不稳定中间体前列腺素H2（PGH2）的非酶降解产物，因为这两种化合物仅在匀浆系统中产生并占环氧化酶代谢产物的很大比例；在其他细胞中也是如此。虽然前列腺素的产生涉及三个步骤，即游离花生四烯酸的释放、PGH合酶（环氧化酶）产生PGH2以及特定异构酶或合成酶将PGH2转化为各种前列腺素，但直到最近，第一步，即游离花生四烯酸的释放，一直被认为是调节前列腺素合成的唯一重要步骤。这一推测基于以下观察结果。只有游离形式的花生四烯酸可转化为前列腺素，并且与磷脂中的酯化形式相比，细胞内游离花生四烯酸池非常小。游离花生四烯酸池的大小由磷脂酶从磷脂中释放以及重新酰化进入磷脂之间的平衡来调节。当静止细胞受到刺激时，花生四烯酸的释放和前列腺素的产生会同时增加。然而，本研究表明，前列腺素合成的所有三个步骤在FRTL-5大鼠甲状腺细胞中均受到调节控制，并且这种控制是一个涉及TSH、胰岛素/胰岛素样生长因子-I（IGF-I）和血清的复杂过程。第一步主要受TSH控制。TSH增加花生四烯酸的合成，并且与去甲肾上腺素一样（5,6），通过一种涉及百日咳毒素敏感G蛋白的机制诱导花生四烯酸从细胞中释放。第二步的调节可以通过测量环氧化酶活性来估计。本报告表明，TSH增加环氧化酶活性，可能是通过增加基因表达，但TSH对环氧化酶活性的影响需要胰岛素/IGF-I或血清。这一结果与关于TSH和胰岛素/IGF-I对FRTL-5甲状腺细胞中糖胺聚糖合成、甲状腺球蛋白合成和生长的影响的研究相似。（摘要截断于400字）
