Pawlikowski M, Lawnicka H, Pisarek H, Kunert-Radek J, Radek M, Culler M D
Department of Neuroendocrinology, Chair of Endocrinology, Medical University of Lodz, Poland.
J Physiol Pharmacol. 2007 Mar;58(1):179-88.
The aim of the study was to examine the effect of somatostatin (SST) and its analogs on the release of chromogranin A (CgA) and alpha-subunit (alpha-SU) from clinically non-functioning pituitary adenomas incubated in vitro. Seven pituitary macroadenomas surgically removed were investigated. All of the tumors were diagnosed before surgery as non-functioning, but they expressed either gonadotropins or their subunits as detected by immunohistochemistry. Two tumors additionally expressed prolactin and growth hormone. All adenomas also expressed chromogranin A (CgA) and at least 3 of 5 subtypes of somatostatin receptors. The cells isolated from the examined tumors were exposed in vitro to either native SST-14 or the following receptor-specific SST analogs: BIM-23926 (agonist of sst1 receptor), BIM-23120 (agonist of sst2 receptor), BIM-23206 (agonist of sst5 receptor) and BIM23A387 (somatostatin/dopamine chimera). The concentration of CgA was measured by means of ELISA method and of alpha-SU was measured by an immunoradiometric method. It was found that the exposure on SST-14 resulted in the decrease of CgA and alpha-SU release from tumor cells in majority of samples, and the effect on CgA was positively correlated with the expression of sst3 and also with the sst2A/sst2B expressions ratio. The inhibitory effect of SST-14 on CgA and alpha-SU seems also to correlate negatively with the expression of sst2B. CgA inhibition also correlates positively with sst5 expression. Among the other compounds studied, only the sst2 agonist decreased the release in all the investigated samples. The remaining substances (agonists of sst1 and sst5 and SST/DA chimera) produced the divergent changes (increased or decreased release, depending on the sample). The data suggest that the inhibition of CgA (and possibly of alpha-SU) release by SST is mediated via subtypes sst2A, sst3 and sst5, whereas sst2B subtype may induce the opposite effect.
本研究旨在探讨生长抑素（SST）及其类似物对体外培养的临床无功能垂体腺瘤中嗜铬粒蛋白A（CgA）和α亚基（α-SU）释放的影响。研究了7例手术切除的垂体大腺瘤。所有肿瘤术前均诊断为无功能，但免疫组化检测发现它们表达促性腺激素或其亚基。另外有2例肿瘤还表达催乳素和生长激素。所有腺瘤均表达嗜铬粒蛋白A（CgA）和生长抑素受体5种亚型中的至少3种。从所检查的肿瘤中分离出的细胞在体外分别暴露于天然SST-14或以下受体特异性SST类似物：BIM-23926（sst1受体激动剂）、BIM-23120（sst2受体激动剂）、BIM-23206（sst5受体激动剂）和BIM23A387（生长抑素/多巴胺嵌合体）。采用酶联免疫吸附测定法（ELISA）测定CgA浓度，采用免疫放射测定法测定α-SU浓度。结果发现，在大多数样本中，暴露于SST-14会导致肿瘤细胞中CgA和α-SU释放减少，对CgA的影响与sst3的表达以及sst2A/sst2B表达比值呈正相关。SST-14对CgA和α-SU的抑制作用似乎也与sst2B的表达呈负相关。CgA的抑制作用也与sst5的表达呈正相关。在所研究的其他化合物中，只有sst2激动剂在所有研究样本中均降低了释放量。其余物质（sst1和sst5激动剂以及SST/DA嵌合体）产生了不同的变化（释放量增加或减少，取决于样本）。数据表明，SST对CgA（可能还有α-SU）释放的抑制作用是通过sst2A、sst3和sst5亚型介导的，而sst2B亚型可能产生相反的作用。
