Cugini C D, Millard W J, Leidy J W
Veterans Affairs Medical Center, West Virginia.
Endocrinology. 1991 Sep;129(3):1355-62. doi: 10.1210/endo-129-3-1355.
The role of signal transduction systems was examined in the secretion of GH-releasing hormone (GHRH) and somatostatin (SS) from perifused rat hypothalamic fragments. Forskolin, an adenylate cyclase activator, stimulated the release of GHRH and SS in a concentration-dependent manner (10-100 microM) with greatest stimulation for GHRH at 100 microM (mean +/- SE, 249 +/- 14%) and for SS at 30 microM (172 +/- 18%). (Bu)2cAMP also augmented GHRH and SS release. The protein kinase-C activator phorbol 12-myristate 13-acetate did not significantly stimulate basal GHRH or SS release at concentrations of 10 nM to 1 microM. The calcium ionophore A23187 enhanced the release of GHRH and SS in a concentration-dependent manner (2-20 microM), with the greatest responses of 282 +/- 50% at 10 microM and 189 +/- 24% at 20 microM, respectively. Potentiation by phorbol 12-myristate 13-acetate of forskolin-stimulated GHRH and SS release was observed. A23187 at 10 microM did not enhance forskolin-stimulated GHRH release, but did potentiate forskolin-stimulated SS release in a more than additive response. We conclude that there is 1) cAMP stimulation of hypothalamic GHRH and SS release, 2) a modulating role of protein kinase-C on cAMP-stimulated release of GHRH and SS, 3) a stimulatory role of the calcium messenger system for GHRH and SS release, 4) interaction of the signal pathways with differences in net GHRH and SS responses, and 5) a modulatory effect of protein kinase-C in perifused hypothalamic fragments which differs from the stimulation of basal GHRH and SS release reported in fetal-derived hypothalamic cell cultures. Our observations suggest an important regulatory role of interacting signal transduction systems in the hypothalamic secretion of GHRH and SS.
研究了信号转导系统在经灌流的大鼠下丘脑片段分泌生长激素释放激素（GHRH）和生长抑素（SS）过程中的作用。腺苷酸环化酶激活剂福斯可林以浓度依赖方式（10 - 100微摩尔）刺激GHRH和SS的释放，在100微摩尔时对GHRH的刺激作用最强（平均值±标准误，249±14%），在30微摩尔时对SS的刺激作用最强（172±18%）。双丁酰环磷腺苷（Bu）2cAMP也增加了GHRH和SS的释放。蛋白激酶C激活剂佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯在10纳摩尔至1微摩尔浓度下未显著刺激基础GHRH或SS的释放。钙离子载体A23187以浓度依赖方式（2 - 20微摩尔）增强GHRH和SS的释放，在10微摩尔时最大反应为282±50%，在20微摩尔时为189±24%。观察到佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯对福斯可林刺激的GHRH和SS释放有增强作用。10微摩尔的A23187未增强福斯可林刺激的GHRH释放，但以超过相加的反应增强了福斯可林刺激的SS释放。我们得出结论：1）环磷酸腺苷（cAMP）刺激下丘脑GHRH和SS的释放；2）蛋白激酶C对cAMP刺激的GHRH和SS释放起调节作用；3）钙信使系统对GHRH和SS的释放起刺激作用；4）信号通路相互作用，对GHRH和SS的净反应存在差异；5）蛋白激酶C在经灌流的下丘脑片段中具有调节作用，这与胎儿来源的下丘脑细胞培养中报道的对基础GHRH和SS释放的刺激作用不同。我们的观察结果表明，相互作用的信号转导系统在下丘脑分泌GHRH和SS过程中起重要调节作用。
