Differential involvement of signaling pathways in the regulation of growth hormone release by somatostatin and growth hormone-releasing hormone in orange-spotted grouper (Epinephelus coioides)

Differential involvement of signaling pathways in the regulation of growth hormone release by somatostatin and growth hormone-releasing hormone in orange-spotted grouper (Epinephelus coioides)
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DOI:
10.1016/j.mce.2013.10.025
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发表时间:
2014-02
影响因子:
4.1
通讯作者:
Bin Wang;Chaobin Qin;Cong Zhang;Jirong Jia;Caiyun Sun;Wensheng Li
Bin Wang;Chaobin Qin;Cong Zhang;Jirong Jia;Caiyun Sun;Wensheng Li
中科院分区:
医学2区
文献类型:
--
作者:
Bin Wang;Chaobin Qin;Cong Zhang;Jirong Jia;Caiyun Sun;Wensheng Li

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生长抑素是最有效的生长激素释放抑制剂,而GHRH是最近发现的硬骨鱼类主要的生长激素释放因子之一。在这项研究中,我们分析了SRIF和GHRH诱导的GH释放调节机制中可能涉及的细胞内转导途径。使用药理学方法,PLC/IP/PKC通路的阻断逆转了SRIF诱导的GH释放抑制,但不影响GHRH诱导的GH释放刺激。此外,SRIF减少两种PKC激活剂诱导的GH释放。AC/cAMP/PKA通路的抑制剂逆转了SRIF和GHRH诱导的对GH释放的影响。此外,SRIF完全消除了由forskolin和8-Br-cAMP引起的GH释放。NOS/NO通路的阻断减弱了GHRH诱导的GH释放,但对SRIF的抑制作用影响甚微。此外,sGC/cGMP途径的抑制剂并没有改变SRIF或GHRH诱导的GH释放调节。总之,这些发现表明SRIF诱导的GH释放抑制是由PLC/IP/PKC和AC/cAMP/PKA途径介导的,而不是由NOS/NO/sGC/cGMP途径介导的。相反,GHRH诱导的GH分泌刺激是由AC/cAMP/PKA和NOS/NO途径介导的,并且不依赖于sGC/cGMP途径和PLC/IP/PKC系统。
Somatostatin is the most effective inhibitor of GH release, and GHRH was recently identified as one of the primary GH-releasing factors in teleosts. In this study, we analyzed the possible intracellular transduction pathways that are involved in the mechanisms induced by SRIF and GHRH to regulate GH release. Using a pharmacological approach, the blockade of the PLC/IP/PKC pathway reversed the SRIF-induced inhibition of GH release but did not affect the GHRH-induced stimulation of GH release. Furthermore, SRIF reduced the GH release induced by two PKC activators. Inhibitors of the AC/cAMP/PKA pathway reversed both the SRIF- and GHRH-induced effects on GH release. Moreover, the GH release evoked by forskolin and 8-Br-cAMP were completely abolished by SRIF. The blockade of the NOS/NO pathway attenuated the GHRH-induced GH release but had minimal effects on the inhibitory actions of SRIF. In addition, inhibitors of the sGC/cGMP pathway did not modify the SRIF- or GHRH-induced regulation of GH release. Taken together, these findings indicate that the SRIF-induced inhibition of GH release is mediated by both the PLC/IP/PKC and the AC/cAMP/PKA pathways and not by the NOS/NO/sGC/cGMP pathway. In contrast, the GHRH-induced stimulation of GH secretion is mediated by both the AC/cAMP/PKA and the NOS/NO pathways and is independent of the sGC/cGMP pathway and the PLC/IP/PKC system.