Jaquet P, Ouafik L, Saveanu A, Gunz G, Fina F, Dufour H, Culler M D, Moreau J P, Enjalbert A
Interactions Cellulaires en Neuroendocrinologie, Unite Mixte de Recherche, UMR 6544, Centre National de la Recherche Scientifique, Marseille, France.
J Clin Endocrinol Metab. 1999 Sep;84(9):3268-76. doi: 10.1210/jcem.84.9.5962.
Recently, it was demonstrated that somatostatin analogs preferential for the SSTR5 subtype suppress PRL release from prolactinoma cell cultures by 30-40%. These data supported the idea of somatostatin receptor subtype-specific control of PRL secretion in such tumors. The present study examines the quantitative profile of SSTRs messenger ribonucleic acid (mRNA) in 10 PRL-secreting tumors and correlates the expression with the ability of native somatostatins (SS14 and SS28), SSTR2 preferential analogs (octreotide and BIM-23197), and the SSTR5 preferential analog BIM-23268 to suppress PRL secretion. RT-PCR quantitative analysis showed a large predominance of SSTR5 mRNA [5648 +/- 1918 pg/pg glyceraldehyde-3-phosphate dehydrogenase (GAPDH)] vs. SSTR2 mRNA (148 +/- 83 pg/pg GAPDH). The SSTR1 transcript was also highly expressed in prolactinomas (1296 +/- 669 pg/pg GAPDH). SSTR5 mRNA expression correlated with PRL inhibition induced by both SRIF14 and SRIF28. Among the different analogs tested, only BIM-23268 produced inhibition of PRL release similar to that achieved with the native peptides. Its EC50 for PRL suppression was 0.28 +/- 0.10 nmol/L. No additive effects on PRL suppression were achieved by cotreatment of the tumor cells with SSTR2 and SSTR5 preferential analogs. In the same tumor cell cultures, quinagolide, a potent dopamine agonist, produced a dose-dependent inhibition of PRL with an EC50 at least 10 times lower than that of BIM-23268. Coincubation of quinagolide and BIM-23268, particularly in tumor cells resistant to dopamine agonist treatment, did not produce additive effects on PRL suppression. In conclusion, prolactinomas have a specific pattern of SSTR subtype mRNA expression (SSTR5 and SSTR1). SSTR5 expression is correlated to PRL regulation. These inhibitory effects are superimposable, at a higher concentration, to those of the dopamine agonists, but are not additive, particularly in the adenomas resistant to dopaminergic suppression of PRL release.
最近的研究表明，对SSTR5亚型具有选择性的生长抑素类似物可使催乳素瘤细胞培养物中的PRL释放量减少30%-40%。这些数据支持了生长抑素受体亚型特异性控制此类肿瘤中PRL分泌的观点。本研究检测了10例分泌PRL的肿瘤中生长抑素受体（SSTR）信使核糖核酸（mRNA）的定量情况，并将其表达与天然生长抑素（SS14和SS28）、SSTR2选择性类似物（奥曲肽和BIM-23197）以及SSTR5选择性类似物BIM-23268抑制PRL分泌的能力进行了关联分析。逆转录聚合酶链反应（RT-PCR）定量分析显示，与SSTR2 mRNA（148±83 pg/pg甘油醛-3-磷酸脱氢酶（GAPDH））相比，SSTR5 mRNA（5648±1918 pg/pg GAPDH）占主导地位。SSTR1转录本在催乳素瘤中也高度表达（1296±669 pg/pg GAPDH）。SSTR5 mRNA表达与SRIF14和SRIF28诱导的PRL抑制相关。在所测试的不同类似物中，只有BIM-23268对PRL释放的抑制作用与天然肽相似。其抑制PRL的半数有效浓度（EC50）为0.28±0.10 nmol/L。用SSTR2和SSTR5选择性类似物共同处理肿瘤细胞，对PRL抑制没有叠加效应。在相同的肿瘤细胞培养物中，强效多巴胺激动剂喹高利特对PRL产生剂量依赖性抑制，其EC50至少比BIM-23268低10倍。喹高利特和BIM-23268共同孵育，特别是在对多巴胺激动剂治疗耐药的肿瘤细胞中，对PRL抑制没有产生叠加效应。总之，催乳素瘤具有特定的SSTR亚型mRNA表达模式（SSTR5和SSTR1）。SSTR5表达与PRL调节相关。这些抑制作用在较高浓度下与多巴胺激动剂的作用相当，但不具有叠加性，尤其是在对多巴胺能抑制PRL释放耐药的腺瘤中。
