Somatostatin receptors 2 and 5 are the major somatostatin receptors in insulinomas:: An in vivo and in vitro study
Somatostatin receptors 2 and 5 are the major somatostatin receptors in insulinomas:: An in vivo and in vitro study
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DOI：
10.1210/jc.2002-021895
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发表时间：
2003-11-01
影响因子：
5.8
通讯作者：
Epelbaum, J
中科院分区：
文献类型：
--
作者：
Bertherat, J;Tenenbaum, F;Epelbaum, J
生长抑素（SRIF）受体（sst）存在于正常胰腺内分泌β细胞上。然而，SRIF类似物在胰岛素瘤的血管造影成像和这些肿瘤的医学管理中的使用似乎仅限于一个亚组的患者。本研究的目的是确定体外sst表达的普遍性，并描述胰岛素瘤中sst亚型结合及其与体内sst受体荧光图（SRS）的相关性。对来自25名患者的27个胰岛素瘤进行了体外研究：22名为良性肿瘤，3名为恶性肿瘤。对其中20例胰岛素瘤进行了sst mRNA的半定量RT-PCR。Sst 2和Sst 5在70%的肿瘤中表达，Sst 1在50%的肿瘤中表达，而Sst 3和Sst 4亚型仅在15-20%的肿瘤中表达。在18个胰岛素瘤中，通过定量放射自显影评估了（125）I-Tyr（0）DTrp（8）SRIF（14）结合，并使用SRIF（14）和L797-591、L779-976、L796-778、L 803 -087、L 817 -818（5种sst亚型的选择性激动剂）以及BIM 23244（sst 2和sst 5的选择性激动剂）进行了竞争实验。在72%的胰岛素瘤中观察到显著的特异性结合。置换实验与每个SST受体的亲和力更高的配体显示显着的结合与SST 2和SST 5配体在72%，SST 3在44%，SST 1在44%，SST 4在28%的情况下。所有显示sst 2结合的胰岛素瘤也对sst 5敏感。然而，sst 5/sst 2置换的比率是可变的，并且仅等于在使用sst 2/sst 5激动剂BIM 23244的实验中SRIF 14的比率。SRS在9名患者中进行了10次;它检测到60%的肿瘤，包括恶性胰岛素瘤的转移。SRS检测到的所有肿瘤均显示高水平的（125）I-Tyr（0）DTrp（8）SRIF（14）结合。三分之一的胰岛素瘤中sst 2/sst 5表达缺失的机制仍有待确定，但这种表达缺失可能与β细胞功能障碍有关。
Somatostatin (SRIF) receptors (sst) are present on normal pancreatic endocrine beta-cells. However, the use of SRIF analogs in the scintigraphic imaging of insulinomas and in the medical management of these tumors seems to be restricted to a subgroup of patients. The aim of this study was to determine the prevalence of sst expression in vitro and characterize sst subtype binding in insulinomas and its correlation with in vivo sst receptor scintigraphy (SRS). In vitro studies were performed on 27 insulinomas from 25 patients: 22 with benign and three with malignant tumors. Semiquantitative RT-PCR of sst mRNAs was performed for 20 of these insulinomas. Sst2 and sst5 were expressed in 70%, sst1 in 50%, and sst3 and sst4 subtypes only in 15-20% of the tumors. (125)I-Tyr(0)DTrp(8)SRIF(14)-binding was assessed by quantitative autoradiography in 18 insulinomas, and competition experiments were performed with SRIF(14) and L797-591, L779-976, L796-778, L803-087, L817-818, selective agonists of the five sst subtypes, and BIM23244, a selective agonist of sst2 and sst5. Significant specific binding was observed in 72% of the insulinomas. Displacement experiments with ligands of higher affinity for each of the sst receptors revealed significant binding with the sst2 and sst5 ligands in 72%, sst3 in 44%, sst1 in 44%, and sst4 in 28% of cases. All insulinomas displaying sst2 binding were also sst5 sensitive. However, the ratio of sst5/sst2 displacement was variable and only equal to that for SRIF14 in experiments with the sst2/sst5 agonist BIM23244. SRS was performed 10 times in nine patients; it detected 60% of the tumors, including metastases of a malignant insulinoma. All the tumors detected by SRS displayed high levels of (125)I-Tyr(0)DTrp(8)SRIF(14) binding. The mechanisms underlying the loss of expression of sst2/sst5 in a third of insulinomas remains to be determined, but this loss of expression may be involved in beta-cell dysfunction.