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选择性sst1、sst2、sst5生长抑素受体激动剂、一种生长抑素/多巴胺(SST/DA)嵌合体及溴隐亭对“临床无功能”垂体腺瘤的体外作用

The effect of selective sst1, sst2, sst5 somatostatin receptors agonists, a somatostatin/dopamine (SST/DA) chimera and bromocriptine on the "clinically non-functioning" pituitary adenomas in vitro.

作者信息

Gruszka A, Kunert-Radek J, Radek A, Pisarek H, Taylor J, Dong J Z, Culler M D, Pawlikowski M

机构信息

Chair of Endocrinology, Medical University of Lodz, Poland.

出版信息

Life Sci. 2006 Jan 11;78(7):689-93. doi: 10.1016/j.lfs.2005.05.061. Epub 2005 Aug 22.

Abstract

The aim of the work was to investigate the effects of somatostatin analogs acting selectively on sst1 (BIM-23926), sst2 (BIM-23120) and sst5 (BIM-23206) receptor subtypes on the viability of "clinically non-functioning" pituitary adenomas in vitro. The effects of native SST (SST-14), a SST/DA chimera (BIM-23A387) and a D(2)-dopamine receptor agonist bromocriptine (BC) were also examined. The study was performed on 10 surgically removed pituitary macroadenomas, diagnosed before surgery as "non-functioning". A part of each tumor was mechanically dispersed and digested with collagenase to isolate the tumoral cells. Another part of each tumor was fixed, embedded in paraffin and immunostained to reveal the pituitary hormones and SST receptor subtypes (sst1, sst2A, sst2B, sst3, sst4, sst5). The tumoral cell suspensions were incubated for 24 h with the substances mentioned above. The quantity of viable cells was estimated using the EZ4U system. The results were compared with the immunohistochemical evaluation of the hormonal profile of adenoma and the sst receptor subtype immunoreactivities present. The findings indicate that selective sst1, sst2 and sst5 receptors agonists, SST/DA chimera and D(2)-dopamine receptor agonist bromocriptine affect the viability of some, but not all, "clinically non-functioning" pituitary adenomas in vitro. The most effective was bromocriptine. The investigated somatostatin analogs including SST/DA chimera exerted roughly similar inhibitory effects. Further studies are needed to fully evaluate the potential usefulness of these compounds in the pharmacological treatment of "non-functioning" pituitary tumors.

摘要

这项工作的目的是研究选择性作用于sst1(BIM - 23926)、sst2(BIM - 23120)和sst5(BIM - 23206)受体亚型的生长抑素类似物对“临床无功能”垂体腺瘤体外生存能力的影响。同时也检测了天然生长抑素(SST - 14)、一种SST/多巴胺嵌合体(BIM - 23A387)和D(2)-多巴胺受体激动剂溴隐亭(BC)的作用。该研究对10例手术切除的垂体大腺瘤进行,术前诊断为“无功能”。将每个肿瘤的一部分进行机械分散并用胶原酶消化以分离肿瘤细胞。每个肿瘤的另一部分进行固定、石蜡包埋和免疫染色,以显示垂体激素和SST受体亚型(sst1、sst2A、sst2B、sst3、sst4、sst5)。将肿瘤细胞悬液与上述物质孵育24小时。使用EZ4U系统评估活细胞数量。将结果与腺瘤激素谱的免疫组织化学评估以及存在的sst受体亚型免疫反应性进行比较。研究结果表明,选择性sst1、sst2和sst5受体激动剂、SST/多巴胺嵌合体和D(2)-多巴胺受体激动剂溴隐亭在体外影响一些但并非所有“临床无功能”垂体腺瘤的生存能力。最有效的是溴隐亭。所研究的生长抑素类似物包括SST/多巴胺嵌合体发挥了大致相似的抑制作用。需要进一步研究以充分评估这些化合物在“无功能”垂体肿瘤药物治疗中的潜在用途。

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