Davis J R, Sheppard M C
J Endocrinol. 1986 Jun;109(3):365-9. doi: 10.1677/joe.0.1090365.
We have studied the effects of cyclic AMP (cAMP) on TSH secretion by cultured rat pituitary cells, using forskolin and dibutyryl cAMP (dbcAMP) to raise the cellular cAMP content by different mechanisms. Forskolin (10 mumol/l), a stimulator of adenylate cyclase, raised the cAMP content within 10 min, but had a more delayed effect on TSH release, with no significant stimulation for at least 6 h, but a clear dose-dependent effect at 24 h. Incubation with dbcAMP likewise increased TSH release after 6-24 h. By contrast, high cellular cAMP levels induced by either forskolin or dbcAMP augmented the TSH response to TRH at an early stage, before any detectable change in unstimulated TSH release. Pretreatment of cells with forskolin led to a parallel upward shift in the subsequent TRH dose-response curve, without a significant change in median effective dose or any change in cellular TSH content. These findings suggest that cAMP acts to increase the availability of TSH for acute release by TRH by modulation of an intracellular releasable hormone pool, and indicate synergistic interactions between the adenylate cyclase system and the phospholipid-calcium stimulus-release coupling mechanism of TRH.
我们利用福斯可林和二丁酰环磷腺苷（dbcAMP）通过不同机制提高细胞内环磷腺苷（cAMP）含量，研究了cAMP对培养的大鼠垂体细胞促甲状腺激素（TSH）分泌的影响。腺苷酸环化酶刺激剂福斯可林（10 μmol/L）在10分钟内提高了cAMP含量，但对TSH释放的影响更为延迟，至少6小时内无明显刺激作用，但在24小时时有明显的剂量依赖性效应。与dbcAMP孵育同样在6 - 24小时后增加了TSH释放。相比之下，福斯可林或dbcAMP诱导的高细胞cAMP水平在未刺激的TSH释放出现任何可检测变化之前的早期阶段增强了TSH对促甲状腺激素释放激素（TRH）的反应。用福斯可林预处理细胞导致随后的TRH剂量 - 反应曲线平行向上移动，半数有效剂量无显著变化，细胞TSH含量也无任何变化。这些发现表明，cAMP通过调节细胞内可释放激素池来增加TRH急性释放时TSH的可用性，并表明腺苷酸环化酶系统与TRH的磷脂 - 钙刺激 - 释放偶联机制之间存在协同相互作用。
