SIGNAL TRANSDUCTION SYSTEMS IN GROWTH HORMONE-RELEASING HORMONE AND SOMATOSTATIN RELEASE FROM PERIFUSED RAT HYPOTHALAMIC FRAGMENTS
SIGNAL TRANSDUCTION SYSTEMS IN GROWTH HORMONE-RELEASING HORMONE AND SOMATOSTATIN RELEASE FROM PERIFUSED RAT HYPOTHALAMIC FRAGMENTS
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DOI：
10.1210/endo-129-3-1355
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发表时间：
1991-09-01
期刊：
影响因子：
4.8
通讯作者：
LEIDY, JW
中科院分区：
文献类型：
--
作者：
CUGINI, CD;MILLARD, WJ;LEIDY, JW
本文研究了灌流大鼠下丘脑碎片分泌生长激素释放激素（GHRH）和生长抑素（SS）的信号转导系统的作用。 Forskolin是一种腺苷酸环化酶激活剂，以浓度依赖性方式（10-100 μ M）刺激GHRH和SS的释放，其中100 μ M对GHRH的刺激最大（平均值+/- SE，249 +/- 14%），30 μ M对SS的刺激最大（172 +/- 18%）。 （Bu）2cAMP也促进GHRH和SS的释放。 蛋白激酶C激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯在10 nM至1 μ M的浓度下没有显著刺激基础GHRH或SS释放。 钙离子载体A23187以浓度依赖性方式（2-20 μ M）增强GHRH和SS的释放，在10 μ M和20 μ M时的最大响应分别为282 +/- 50%和189 +/- 24%。 观察到佛波醇12-肉豆蔻酸酯13-乙酸酯增强毛喉素刺激的GHRH和SS释放。A23187在10 μ M时不增强Forskolin刺激的GHRH释放，但增强Forskolin刺激的SS释放，这是一种超过相加的反应，我们认为：1）cAMP刺激下丘脑GHRH和SS释放，2）蛋白激酶C对cAMP刺激的GHRH和SS释放的调节作用，3）钙信使系统对GHRH和SS释放的刺激作用，4）信号通路的相互作用与净GHRH和SS反应的差异，和5）蛋白激酶-C在灌流的下丘脑片段中的调节作用，其不同于在胎儿来源的下丘脑细胞培养物中报道的基础GHRH和SS释放的刺激。 我们的观察表明，一个重要的调节作用的相互作用的信号转导系统在下丘脑分泌的GHRH和SS。
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-mu-M) with greatest stimulation for GHRH at 100-mu-M (mean +/- SE, 249 +/- 14%) and for SS at 30-mu-M (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-mu-M. The calcium ionophore A23187 enhanced the release of GHRH and SS in a concentration-dependent manner (2-20-mu-M), with the greatest responses of 282 +/- 50% at 10-mu-M and 189 +/- 24% at 20-mu-M, respectively. Potentiation by phorbol 12-myristate 13-acetate of forskolin-stimulated GHRH and SS release was observed. A23187 at 10-mu-M 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.