Involvement of annexin 5 in G protein mediated signal transduction

研究了一种新的G蛋白介导的信号转导机制。明确了膜联蛋白5参与了G蛋白偶联信号转导过程。膜联蛋白是新发现的钙磷脂结合蛋白的一员。结果概要如下。从GnRH受体到膜联蛋白5的合成明确了MAPK系统在垂体促性腺激素中GnRH受体和膜联蛋白5 mRNA合成之间的作用。此外，观察到膜联蛋白5在GnRH促进促性腺激素分泌的过程中不可或缺，明确了膜联蛋白5是GnRH受体信号转导的新信号因子2。卵巢膜联蛋白5分析卵巢膜联蛋白5的变化。膜联蛋白5的合成在黄体化后开始，泌乳素抑制膜联蛋白5的表达。阐明了膜联蛋白5是通过抑制泌乳素分泌而在黄体中出现的，其细胞处于凋亡状态。此外，明确了局部GnRH可增强膜联蛋白5的表达并诱导细胞凋亡。睾丸中的膜联蛋白5已被证实分布于各种睾丸细胞。其中，内皮细胞和间质谷被抗膜联蛋白5强烈染色。结果表明，人绒毛膜促性腺激素可增加间质细胞的膜联蛋白5。这种作用被证明是由局部GnRH作用介导的。综上所述，在垂体前叶促性腺细胞、黄体细胞和间质细胞中，膜联蛋白5受GnRH受体的控制。膜联蛋白5是GnRH受体的生物标志物。GnRH受体-膜联蛋白5系统似乎在各种细胞中都有应用。

A new G protein mediated signal transduction mechanism was studied. It was clarified that annexin 5 took part in the G protein coupled signal transduction process. Annexin is a member of newly identified calcium-phospholipid binding proteins. The outline of the results is brought together as follows.1.From GnRH receptor to annexin 5 synthesisIt was clarified that the MAPK system lay between the GnRH receptor and annexin 5 mRNA synthesis in the pituitary gonadotropes. In addition, it was observed that annexin 5 was indispensable to the process that GnRH promotes the gonadotrophin secretion, and clarified that annexin 5 was a new signal factor of the GnRH receptor signal transduction.2.Annexin 5 in the ovaryChanges in ovarian annexin 5 were analyzed. The synthesis of annexin 5 was demonstrated to start after luteinization and the expression of annexin 5 was inhibited by prolactin. It was clarified that annexin 5 appeared in corpus luteum by the inhibition of prolactin secretion and those cells were in apoptosis. In addition, it was clarified that local GnRH enhanced annexin 5 expression and induced apoptosis.3.Annexin 5 in the testisAnnexin 5 was demonstrated to distribute to various testicular cells. Among these, endotherial cells and Leydig dells were intensely stained with anti-annexin 5. It was clarified that annexin 5 of Leydig cells was increased by the administration of human chorinic gonadotropin. This effect was shown to be mediated by the local GnRH action.Getting together, annexin 5 was shown to be under the control of GnRH receptor in the anterior pituitary gonadotropes, luteal cells and Leydig cells. Annexin 5 is a biomarker of GnRH receptor. GnRH receptor-annexin 5 system seems to be utilized in various cell species.