Evidence for a role of protein kinase C in luteinizing hormone synthesis and secretion. Impaired responses to gonadotropin-releasing hormone in protein kinase C-depleted pituitary cells.
Evidence for a role of protein kinase C in luteinizing hormone synthesis and secretion. Impaired responses to gonadotropin-releasing hormone in protein kinase C-depleted pituitary cells.
复制标题
蛋白激酶 C 在黄体生成素合成和分泌中作用的证据。
DOI：
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发表时间：
1988
影响因子：
4.8
通讯作者：
K. Catt
中科院分区：
文献类型：
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作者：
S. Stojilkovic;John P. Chang;D. Ngo;K. Catt
蛋白激酶C在促黄体生成素（LH）释放中的作用进行了分析，在正常和蛋白激酶C（Ca 2 +/磷脂依赖酶）耗尽垂体细胞培养的佛波醇酯和促性腺激素释放激素（GnRH）的行动的研究。正常垂体细胞对GnRH的LH分泌反应在Ca ~（2+）缺乏的培养基中减少但未被消除，这与GnRH作用的细胞外Ca ~（2+）依赖性和非依赖性成分的存在相一致。这两种成分都可以通过用12-O-十四烷酰基佛波醇13-乙酸酯（TPA）处理而引起。LH分泌的TPA和GnRH的反应是加性的，只有在低剂量和收敛到一个共同的最大值在高浓度的激动剂在存在或不存在细胞外Ca 2+。释放储存的LH由GnRH和TPA伴随着分泌新合成的LH从2至5小时期间的刺激由任何激动剂。促性腺激素释放激素（GnRH）和促性腺激素释放激素（TPA）均能促进LH合成，且呈剂量依赖性，新合成的LH与释放的LH之比接近1：2。TPA引起胞质蛋白激酶C迅速和完全易位到垂体细胞的颗粒部分，随后总酶含量逐渐下降，6小时后约为10%。在洗涤和再孵育15小时后，细胞溶质酶部分恢复（至20%）。这种激酶C耗尽的细胞表现出显着的，剂量依赖性减少的行动，GnRH和TPA LH的释放和合成在正常和Ca 2+缺乏的培养基。这些观察结果支持蛋白激酶C参与垂体促性腺激素细胞LH生物合成和分泌的假设，并参与GnRH对这些过程的作用。
The role of protein kinase C in luteinizing hormone (LH) release was analyzed in studies on the actions of phorbol esters and gonadotropin-releasing hormone (GnRH) in normal and protein kinase C (Ca2+/phospholipid-dependent enzyme)-depleted pituitary cell cultures. LH secretory responses of normal pituitary cells to GnRH were reduced but not abolished in Ca2+-deficient medium, consistent with the existence of extracellular Ca2+-dependent and -independent components of GnRH action. Both of these components could be elicited by treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA). The LH secretory responses to TPA and GnRH were additive only at low doses and converged to a common maximum at high concentrations of the agonists in the presence or absence of extracellular Ca2+. The release of stored LH by GnRH and TPA was accompanied by secretion of newly synthesized LH from 2 to 5 h during stimulation by either of the agonists. LH synthesis was increased in a progressive and dose-dependent manner by GnRH and TPA, and the ratio between newly synthesized and released hormone was near 1:2. TPA caused rapid and complete translocation of cytosolic protein kinase C to the particulate fraction of pituitary cells, followed by a progressive decrease in total enzyme content to approximately 10% after 6 h. Partial recovery of the cytosolic enzyme (to 20%) occurred after washing and reincubation for 15 h. Such kinase C-depleted cells showed prominent, dose-dependent reductions in the actions of GnRH and TPA on LH release and synthesis in both normal and Ca2+-deficient media. These observations support the hypothesis that protein kinase C participates in LH biosynthesis and secretion in pituitary gonadotrophs and is involved in the actions of GnRH upon these processes.