Pasquali Daniela, Notaro Antonio, Bonavolonta' Giulio, Vassallo Patrizia, Bellastella Antonio, Sinisi Antonio Agostino
Istituto di Endocrinologia, Seconda Università di Napoli, Building 16, Via Pansini 5, 80131 Naples, Italy.
J Clin Endocrinol Metab. 2002 Nov;87(11):5125-9. doi: 10.1210/jc.2002-020790.
The radiolabeled somatostatin (SST) analog octreotide accumulates within the orbits of active Graves' ophthalmopathy (GO), and octreotide and lanreotide have been proposed to treat this disorder. It is still unclear which retroorbital cells the SST analogs target. Lymphocytic infiltration of retroorbital tissues is a peculiarity of GO, and labeled octreotide could accumulate at specific sites on retroorbital-activated lymphocytes. The accumulation of radiolabeled analogs is due to the interaction with specific cell surface SST receptors. Five subtypes of somatostatin receptors (SST1-5), member of the G protein-coupled, seven-transmembrane superfamily, are described. It still unknown which SST subtype is expressed in retroorbital activated lymphocytes. The aim of this study was to evaluate the expression of SST1-5 genes in lymphocytes recovered from retroorbital tissues obtained from patients with GO undergoing orbital decompression. Cultured phytohemagglutinin-stimulated lymphocytes from retroorbital blood samples, drawn during orbital surgery in five patients with GO and in two control patients without autoimmune or thyroid diseases and without orbital inflammatory conditions, were also studied. RT-PCR of total RNA extracted from lymphocytes was performed using primers for SST1-5 and, as internal control, for glyceraldehyde-3-phosphate dehydrogenase. All SSTs transcripts were found in lymphocytes both from GO retroorbital tissues and blood samples. The levels of expression of SST1, -2, and -4 mRNA were higher than those of the SST3 and -5 transcripts. In the lymphocytes from control subjects, the SST subtypes with high affinity for octreotide were barely found. The presence, even if at different concentrations, of all SST1-5 receptors in retroorbital lymphocytes from GO shows that they are targeted by SST analogs and could explain the effects described in GO patients treated with SST analogs.
放射性标记的生长抑素(SST)类似物奥曲肽在活动性Graves眼病(GO)的眼眶内聚集,有人提出用奥曲肽和兰瑞肽治疗这种疾病。目前尚不清楚SST类似物靶向哪些眶后细胞。眶后组织的淋巴细胞浸润是GO的一个特点,标记的奥曲肽可能在眶后活化淋巴细胞的特定部位聚集。放射性标记类似物的聚集是由于与特定细胞表面SST受体的相互作用。生长抑素受体(SST1 - 5)有五个亚型,属于G蛋白偶联的七跨膜超家族。目前仍不清楚哪种SST亚型在眶后活化淋巴细胞中表达。本研究的目的是评估从接受眼眶减压的GO患者的眶后组织中回收的淋巴细胞中SST1 - 5基因的表达。还研究了从5例GO患者和2例无自身免疫或甲状腺疾病且无眼眶炎症的对照患者的眼眶手术期间采集的眶后血样中培养的植物血凝素刺激的淋巴细胞。使用针对SST1 - 5的引物以及作为内对照的甘油醛 - 3 - 磷酸脱氢酶引物,对从淋巴细胞中提取的总RNA进行逆转录聚合酶链反应(RT - PCR)。在GO眶后组织和血样的淋巴细胞中均发现了所有SST的转录本。SST1、-2和-4 mRNA的表达水平高于SST3和-5转录本。在对照受试者的淋巴细胞中,几乎未发现对奥曲肽具有高亲和力的SST亚型。GO眶后淋巴细胞中所有SST1 - 5受体的存在,即使浓度不同,表明它们是SST类似物的作用靶点,这可以解释在用SST类似物治疗的GO患者中所描述的效果。