Differential regulation of pituitary hormone secretion and gene expression by thyrotropin-releasing hormone. A role for mitogen-activated protein kinase signaling cascade in rat pituitary GH3 cells
Differential regulation of pituitary hormone secretion and gene expression by thyrotropin-releasing hormone. A role for mitogen-activated protein kinase signaling cascade in rat pituitary GH3 cells
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DOI：
10.1095/biolreprod67.1.107
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发表时间：
2002-07-01
影响因子：
3.6
通讯作者：
Miyamoto, E
中科院分区：
文献类型：
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作者：
Kanasaki, H;Yonehara, T;Miyamoto, E
我们研究了丝裂原激活蛋白（MAP）激酶激活在催乳素和生长激素的分泌过程和基因表达中的可能参与。促甲状腺激素释放激素（TRH）迅速刺激 GH3 细胞分泌催乳素和生长激素。 TRH诱导的分泌不被50μM PD098059抑制，但被1μM渥曼青霉素和10μM KN93完全抑制，表明MAP激酶不介导分泌过程。 TRH 刺激 GH3 细胞显着增加催乳素 mRNA 水平，而生长激素 mRNA 表达则大幅减弱。添加PD098059可抑制TRH刺激的催乳素mRNA的增加，并且PD098059也可抑制生长激素mRNA的减少。用 pFC-MEKK 载体（一种组成型活性 MAP 激酶激酶）转染细胞，显着增加催乳素的合成并减少生长激素的合成。这些数据综合表明 MAP 激酶介导 TRH 诱导的催乳素和生长激素基因表达的调节。报告基因检测显示催乳素启动子活性被TRH增加并且被添加PD098059完全抑制，但生长激素启动子活性未被TRH改变。这些结果表明，TRH 刺激催乳素和生长激素的分泌，但催乳素和生长激素的基因表达受 TRH 的差异调节，并由不同的机制介导。
We examined the possible involvement of mitogen-activated protein (MAP) kinase activation in the secretory process and gene expression of prolactin and growth hormone. Thyrotropin-releasing hormone (TRH) rapidly stimulated the secretion of both prolactin and growth hormone from GH3 cells. Secretion induced by TRH was not inhibited by 50 muM PD098059, but was completely inhibited by 1 muM wortmannin and 10 muM KN93, suggesting that MAP kinase does not mediate the secretory process. Stimulation of GH3 cells with TRH significantly increased the mRNA level of prolactin, whereas expression of growth hormone mRNA was largely attenuated. The increase in prolactin mRNA stimulated by TRH was inhibited by addition of PD098059, and the decrease in growth hormone mRNA was also inhibited by PD098059. Transfection of the cells with a pFC-MEKK vector (a constitutively active MAP kinase kinase kinase), significantly increased the synthesis of prolactin and decreased the synthesis of growth hormone. These data taken together indicate that MAP kinase mediates TRH-induced regulation of prolactin and growth hormone gene expression. Reporter gene assays showed that prolactin promoter activity was increased by TRH and was completely inhibited by addition of PD098059, but that the promoter activity of growth hormone was unchanged by TRH. These results suggest that TRH stimulates both prolactin and growth hormone secretion, but that the gene expressions of prolactin and growth hormone are differentially regulated by TRH and are mediated by different mechanisms.