Luque Raúl M, Durán-Prado Mario, García-Navarro Socorro, Gracia-Navarro Francisco, Kineman Rhonda D, Malagón María M, Castaño Justo P
Department of Cell Biology, Physiology, and Immunology, University of Córdoba, E-14014 Córdoba, Spain.
Endocrinology. 2006 Jun;147(6):2902-8. doi: 10.1210/en.2005-1559. Epub 2006 Mar 16.
It is well established that somatostatin acts through G protein-coupled receptors, termed sst, to inhibit GH release. However in pigs somatostatin can stimulate or inhibit in vitro GH secretion in a dose- and somatotrope subpopulation-dependent manner. We report herein that somatostatin-stimulated GH release is blocked by pretreatment with GTPgamma-S, suggesting an involvement of G protein-coupled receptors. Consistent with this, an sst5 selective agonist stimulated spontaneous GH secretion at doses ranging 10(-13) to 10(-9) m, without influencing GHRH-induced GH release. Conversely, sst1-, sst2-, sst3-, and sst4-specific agonists inhibited GHRH-evoked GH release but not basal GH secretion. Examination of the effects of sst-specific agonists on two subpopulations of somatotrope cells separated by density gradient centrifugation [low- (LD) and high-density (HD) cells] showed that only a low dose of the sst5 agonist stimulated GH release in LD somatotropes, whereas both low and high doses of this agonist stimulated GH release in HD cells. In marked contrast, sst1 and sst2 agonists blocked GHRH-stimulated GH release in LD cells at all doses tested, whereas only a high dose of the sst2 agonist inhibited GHRH-induced GH release in HD somatotropes. Interestingly, sst expression pattern in these subpopulations correlates with the distinct actions of sst-selective agonists; specifically, sst5 is more abundant in HD somatotropes, whereas sst1 and sst2 mRNA predominate in LD cells. These results indicate that in the pig, sst1 and sst2 are the primary mediators of the inhibitory effects of somatostatin, whereas sst5 or an sst5-related mechanism mediates the stimulatory action of somatostatin on GH release.
众所周知，生长抑素通过称为sst的G蛋白偶联受体发挥作用，抑制生长激素（GH）释放。然而，在猪中，生长抑素可以以剂量和生长激素分泌细胞亚群依赖性方式刺激或抑制体外GH分泌。我们在此报告，用GTPγ-S预处理可阻断生长抑素刺激的GH释放，提示G蛋白偶联受体参与其中。与此一致，sst5选择性激动剂在10^(-13)至10^(-9) m的剂量范围内刺激自发性GH分泌，而不影响生长激素释放激素（GHRH）诱导的GH释放。相反，sst1、sst2、sst3和sst4特异性激动剂抑制GHRH诱发的GH释放，但不抑制基础GH分泌。通过密度梯度离心分离的生长激素分泌细胞的两个亚群（低密度（LD）和高密度（HD）细胞）上检测sst特异性激动剂的作用，结果显示，只有低剂量的sst5激动剂刺激LD生长激素分泌细胞释放GH，而该激动剂的低剂量和高剂量均刺激HD细胞释放GH。明显不同的是，在所有测试剂量下，sst1和sst2激动剂均阻断LD细胞中GHRH刺激的GH释放，而只有高剂量的sst2激动剂抑制HD生长激素分泌细胞中GHRH诱导的GH释放。有趣的是，这些亚群中sst的表达模式与sst选择性激动剂的不同作用相关；具体而言，sst5在HD生长激素分泌细胞中更丰富，而sst1和sst2 mRNA在LD细胞中占主导。这些结果表明，在猪中，sst1和sst2是生长抑素抑制作用的主要介质，而sst5或与sst5相关的机制介导生长抑素对GH释放的刺激作用。
