Torjesen P A, Bjøro T, Ostberg B C, Haug E
Hormone Laboratory, Aker Hospital, Oslo, Norway.
Mol Cell Endocrinol. 1988 Mar;56(1-2):107-14. doi: 10.1016/0303-7207(88)90014-7.
In cultured rat pituitary cells (GH4C1 cells) the ability of thyrotropin-releasing hormone (TRH) to stimulate phosphodiesteratic cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) by a phospholipase C-type reaction was confirmed. The dose-response relationship for the TRH-stimulated phospholipase C was elucidated as was the relationship between the various inositol phosphates formed during the first few seconds after stimulation. The TRH-stimulated phospholipase C was subject to desensitization by repeated TRH treatment of cell cultures. This desensitization was dependent on the dose of TRH during preincubation. Following desensitization no decline in the levels of PIP2 was detected, even in the presence of decreased levels of PIP2 precursors. The TRH-stimulated phospholipase C activity was not attenuated following pretreatment with 12-O-tetradecanoylphorbol 3-acetate (TPA) to stimulate protein kinase C activity, and TRH also induced desensitization in the presence of the protein kinase C inhibitor polymyxin B. Thus, regulation of protein kinase C activity seemed not to be involved in the desensitization process. It is suggested that the ability of TRH to desensitize its own receptors and their link to phospholipase C, is mediated by the rise in intracellular calcium that is initiated by the TRH-receptor interaction.
在培养的大鼠垂体细胞（GH4C1细胞）中，促甲状腺激素释放激素（TRH）通过磷脂酶C型反应刺激磷脂酰肌醇4,5 - 二磷酸（PIP2）磷酸二酯酶裂解的能力得到了证实。阐明了TRH刺激的磷脂酶C的剂量 - 反应关系以及刺激后最初几秒内形成的各种肌醇磷酸之间的关系。通过对细胞培养物进行重复的TRH处理，TRH刺激的磷脂酶C会发生脱敏。这种脱敏取决于预孵育期间TRH的剂量。脱敏后，即使PIP2前体水平降低，也未检测到PIP2水平下降。在用12 - O - 十四烷酰佛波醇3 - 乙酸酯（TPA）预处理以刺激蛋白激酶C活性后，TRH刺激的磷脂酶C活性并未减弱，并且在存在蛋白激酶C抑制剂多粘菌素B的情况下，TRH也会诱导脱敏。因此，蛋白激酶C活性的调节似乎不参与脱敏过程。有人提出，TRH使自身受体脱敏的能力及其与磷脂酶C的联系是由TRH - 受体相互作用引发的细胞内钙升高介导的。
