Eto S, Fleischer N
Endocrinology. 1976 Jan;98(1):114-22. doi: 10.1210/endo-98-1-114.
Studies of TSH release and production were performed in short term monolayer cultures of transplantable, thyroid hormone responsive, thyrotropin (TSH) producing mouse pituitary tumors. These tumors contained large amounts of TSH, small amounts of growth hormone (GH) and no detectable luteinizing hormone (LH), indicating that the predominant hormone product of tumor cells was TSH. The TSH content per tumor cell was similar to that of the normal pituitary where thyrotrophs represent a small fraction of the total cells, suggesting that the TSH content per tumor cell was less than that of the normal thyrotroph. There was a time dependent release and production of TSH by tumor cells in monolayer culture. Thyrotropin releasing hormone (TRH) increased the release into the media and the production of TSH in a dose dependent manner. Maximum effects were noted at 0.2 ng/ml. Thyroid hormones and somatostatin inhibited both basal and TRH induced effects on both TSH release and production. TSH release as induced by TRH was calcium dependent. TSH release was stimulated by ouabain (10(-3)M) and potassium (57 mM), agents known to promote cellular calcium uptake in a calcium dependent manner. These studies indicate that tumor derived cells function in monolayer culture in a similar fashion to normal thyrotrophs. Studies were conducted to test the hypothesis that TRH action is mediated by adenosine 3',5' monophosphate (cAMP). Dibutyryl cAMP (6 mM) and theophylline (10 mM) increased TSH release suggesting that cAMP is involved in TSH release. However, TRH had no detectable effect on tumor cell adenylate cyclase activity or levels of cAMP. In contrast, PGE1 (1-10 mug/ml) stimulated adenylate cyclase activity and elevated cellular levels of cAMP without increasing TSH release. Thus, we are unable to confirm the postulate that cAMP is the intracellular mediator of TRH action.
在可移植的、对甲状腺激素有反应的、产生促甲状腺激素（TSH）的小鼠垂体肿瘤的短期单层培养物中，进行了TSH释放和产生的研究。这些肿瘤含有大量TSH、少量生长激素（GH）且未检测到促黄体生成素（LH），表明肿瘤细胞的主要激素产物是TSH。每个肿瘤细胞的TSH含量与正常垂体相似，而正常垂体中促甲状腺细胞仅占总细胞的一小部分，这表明每个肿瘤细胞的TSH含量低于正常促甲状腺细胞。单层培养的肿瘤细胞中TSH的释放和产生存在时间依赖性。促甲状腺激素释放激素（TRH）以剂量依赖性方式增加了培养基中TSH的释放和TSH的产生。在0.2 ng/ml时观察到最大效应。甲状腺激素和生长抑素抑制基础状态以及TRH诱导的对TSH释放和产生的影响。TRH诱导的TSH释放是钙依赖性的。哇巴因（10⁻³M）和钾（57 mM）刺激了TSH释放，已知这些试剂以钙依赖性方式促进细胞对钙的摄取。这些研究表明，肿瘤来源的细胞在单层培养中的功能与正常促甲状腺细胞相似。进行了研究以检验TRH作用由3',5'-环磷酸腺苷（cAMP）介导的假说。二丁酰cAMP（6 mM）和茶碱（10 mM）增加了TSH释放，表明cAMP参与TSH释放。然而，TRH对肿瘤细胞腺苷酸环化酶活性或cAMP水平没有可检测到的影响。相反，前列腺素E1（1 - 10 μg/ml）刺激了腺苷酸环化酶活性并提高了细胞内cAMP水平，但没有增加TSH释放。因此，我们无法证实cAMP是TRH作用的细胞内介质这一假设。
