Lippes H A, Spaulding S W
Endocrinology. 1986 Apr;118(4):1306-11. doi: 10.1210/endo-118-4-1306.
We have determined the effects of tetradecanoyl phorbol acetate (TPA) and of the calcium ionophore A23187 on two thyroid responses to TSH previously reported to be cAMP-independent. We observed that TPA and A23187, at doses of 1.0 microM, stimulated both hydrogen peroxide generation and glucose oxidation in calf thyroid slices. A subthreshold dose of A23187 (0.1 microM) added to a submaximal dose of TPA (0.5 microM) acted synergistically, stimulating H2O2 production to the same degree as a maximally effective dose of TSH (50 mU/ml). Forskolin (25 microM), a direct stimulator of adenylate cyclase, actually inhibited both glucose oxidation and hydrogen peroxide generation. Lithium chloride (25 mM) had no effect on either response, either in the basal state or with TSH stimulation. The calcium channel antagonist verapamil (50 microM) decreased the basal activity of glucose oxidation and peroxide generation but did not substantially inhibit the effect of TSH on H2O2 generation under the conditions studied. These data support the concept that TSH induces changes in the thyroid phosphatidylinositol metabolism which activates protein kinase-C (c-kinase) and raises cytosolic free calcium. These events appear to act in concert to mediate certain metabolic responses in differentiated thyroid tissue.
我们已经确定了十四酰佛波醇乙酸酯（TPA）和钙离子载体A23187对先前报道的两种甲状腺对促甲状腺激素（TSH）反应的影响，这两种反应据报道不依赖于环磷酸腺苷（cAMP）。我们观察到，剂量为1.0微摩尔的TPA和A23187可刺激小牛甲状腺切片中的过氧化氢生成和葡萄糖氧化。将亚阈值剂量的A23187（0.1微摩尔）添加到亚最大剂量的TPA（0.5微摩尔）中具有协同作用，可将过氧化氢生成刺激到与最大有效剂量的TSH（50毫单位/毫升）相同的程度。毛喉素（25微摩尔）是腺苷酸环化酶的直接刺激剂，实际上抑制了葡萄糖氧化和过氧化氢生成。氯化锂（25毫摩尔）在基础状态或TSH刺激下对这两种反应均无影响。钙通道拮抗剂维拉帕米（50微摩尔）降低了葡萄糖氧化和过氧化物生成的基础活性，但在所研究的条件下并未实质性抑制TSH对过氧化氢生成的作用。这些数据支持这样的概念，即TSH诱导甲状腺磷脂酰肌醇代谢发生变化，从而激活蛋白激酶-C（c激酶）并提高细胞质游离钙水平。这些事件似乎协同作用，介导分化甲状腺组织中的某些代谢反应。
