STIMULATION OF ADENOSINE-3',5'-MONOPHOSPHATE PRODUCTION BY GROWTH HORMONE-RELEASING FACTOR AND ITS INHIBITION BY SOMATOSTATIN IN ANTERIOR-PITUITARY CELLS-INVITRO
STIMULATION OF ADENOSINE-3',5'-MONOPHOSPHATE PRODUCTION BY GROWTH HORMONE-RELEASING FACTOR AND ITS INHIBITION BY SOMATOSTATIN IN ANTERIOR-PITUITARY CELLS-INVITRO
复制标题
DOI：
10.1210/endo-113-5-1726
复制
发表时间：
1983-01-01
期刊：
影响因子：
4.8
通讯作者：
VALE, WW
中科院分区：
文献类型：
--
作者：
BILEZIKJIAN, LM;VALE, WW
合成GRF[GH释放因子](HpGRF)刺激垂体前叶GH[GH]分泌，与cAMP的快速增加有关。在培养的大鼠垂体前叶细胞中加入1 nM hpGRF 5分钟内，细胞内cAMP水平升高6倍，并在30分钟时达到最大反应。胞外培养上清液中cAMP的积累也被这种多肽增强。比较不同浓度的hpGRF对两种细胞反应(GH分泌和cAMP形成)的影响，发现hpGRF需要比GH分泌多10倍的hpGRF才能获得对cAMP产生的半最大刺激。生长抑素完全阻断hpGRF刺激的GH释放，但在存在或不存在磷酸二酯酶抑制剂的情况下，仅部分抑制cAMP的产生。维拉帕米也抑制hpGRF的GH释放，但与生长抑素不同的是，这种作用与cAMP产生的减少无关，事实上，细胞内cAMP水平在维拉帕米存在下略有增加，表明钙离子是激素释放所必需的，但不是激活腺苷环化酶所必需的。与此一致的是，观察到8-溴-cAMP引起的生长激素释放也被维拉帕米阻断。CoCl2和CdCl2对基础和hpGRF刺激的GH释放的抑制作用进一步表明了对钙的需求。CAMP可能作为GRF作用于生长激素的细胞内介质，而钙离子是该释放过程所必需的。生长抑素可能通过干扰cAMP的产生或作用于cAMP产生后的分泌过程而对GH的分泌产生抑制作用。
The stimulation of GH [growth hormone] secretion from the anterior pituitary by synthetic GRF [GH-releasing factor] (hpGRF) is associated with a rapid increase in cAMP production. Within 5 min of the addition of 1 nM hpGRF to cultured rat anterior pituitary cells, intracellular cAMP levels are elevated 6-fold, with a maximal response being observed at 30 min. cAMP accumulation in the extracellular medium is also enhanced by this peptide. Comparison of the 2 cellular responses (GH secretion and cAMP formation) at various concentrations of hpGRF indicates that 10 times more hpGRF is required to obtain half-maximal stimulation of cAMP production than for GH secretion. Somatostatin totally blocks hpGRF-stimulated GH release, but only partially attenuates cAMP production in the presence or absence of a phosphodiesterase inhibitor. Verapamil also inhibits GH release in response to hpGRF, but, unlike somatostatin, this effect is not associated with an attenuation of cAMP production, in fact, intracellular cAMP levels are slightly augmented in the presence of verapamil, indicating that Ca2+ is required for hormone release but not for the activation of adenylate cyclase. Consistent with this is the observation that the release of GH due to 8-bromo-cAMP is also blocked by verapamil. A requirement for Ca2+ is further indicated by the inhibitory effects of CoCl2 and CdCl2 on both basal and hpGRF-stimulated GH release. cAMP may play a role as an intracellular mediator of GRF action in somatotrophs and that Ca2+ is required for the release process. Somatostatin may exert its inhibitory effects on GH secretion either by interfering with cAMP production or by an action on the secretory process subsequent to cAMP production.