Human somatostatin receptor subtypes in acromegaly: Distinct patterns of messenger ribonucleic acid expression and hormone suppression identify different tumoral phenotypes
Human somatostatin receptor subtypes in acromegaly: Distinct patterns of messenger ribonucleic acid expression and hormone suppression identify different tumoral phenotypes
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DOI：
10.1210/jc.85.2.781
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发表时间：
2000-02-01
影响因子：
5.8
通讯作者：
Ouafik, LH
中科院分区：
文献类型：
--
作者：
Jaquet, P;Saveanu, A;Ouafik, LH
最近，使用生长抑素（SRIF）受体2（SSTR 2）或SSTR 5亚型的优先类似物的研究表明，从GH分泌的人腺瘤的GH和PRL释放的可变抑制。这些数据提示了SSTR亚型特异性的概念。在本研究中，5个SSTR亚型的信使核糖核酸（mRNA）的定量表达和SRIF 14，SRIF 28，奥曲肽，SSTR 2-优先类似物，BIM-23197，和SSTR 5-优先类似物，BIM-23268，GH和PRL分泌的抑制作用进行了分析，从15肢端肥大症肿瘤培养的细胞。RT-PCR分析显示SSTR 2和SSTR 5 mRNA表达的一致模式。SSTR 5 mRNA的表达水平（1052 +/-405 pg/pg甘油醛-3-磷酸脱氢酶）高于SSTR 2 mRNA（100 +/-30 pg/pg甘油醛-3-磷酸脱氢酶）。然而，只有SSTR 2 mRNA表达与SRIF 14、SRIF 28和BIM-23197诱导的GH抑制程度相关。在10例同时分泌GH和PRL的混合腺瘤中，RT-PCR分析显示SSTR 5、SSTR 2和SSTR 1 mRNA的共表达。在所有情况下，SRIF 14、SRIF 28和SSTR 5优先类似物BIM-23268显著抑制PRL分泌，平均最大抑制为48 +/-4%。相比之下，SSTR 2-优先类似物，BIM-23197和奥曲肽，在10例中仅6例有效抑制PRL。在从对SRIF类似物奥曲肽部分响应的患者中采集的腺瘤培养的细胞中，当组合测试SSTR 2和SSTR 5偏好类似物BIM-23197和BIM-23268时，观察到抑制GH和PRL分泌的部分加和性。我们的数据显示，根据肿瘤，SSTR 2和SSTR 5转录物的比例高度可变。SSTR 2-偏好化合物一贯抑制GH释放，而SSTR 5-偏好化合物是PRL分泌的主要抑制剂。当这两种药物联合使用时，在混合GH加PRL分泌腺瘤中观察到的部分加和性可能对此类肿瘤的治疗方法感兴趣。
Recently, studies using somatostatin (SRIF) analogs preferential for either the SRIF receptor 2 (SSTR2) or the SSTR5 subtype demonstrated a variable suppression of GH and PRL release fi om GH-secreting human adenomas. These data suggested the concept of SSTR subtype specificity in such tumors. In the present study the quantitative expression of messenger ribonucleic acid (mRNA) far the 5 SSTR subtypes and the inhibitory effects of SRIF14; SRIF28; octreotide; the SSTR2-preferential analog, BIM-23197; and the SSTR5-preferential analog, BIM-23268, on GH and PRL secretion were analyzed in cells cultured from 15 acromegalic tumors. RT-PCR analysis revealed a consistent pattern of SSTR2 and SSTR5 mRNA expression. SSTR5 mRNA was expressed at a higher level(1052 +/- 405 pg/pg glyceraldehyde-3-phosphate dehydrogenase) than SSTR2 mRNA (100 +/- 30 pg/pg glyceraldehyde-3-phosphate dehydrogenase). However, only SSTR2 mRNA expression correlated with the degree of GH inhibition induced by SRIF14, SRIF28, and BIM-23197. The SSTR5-preferential compound inhibited GH release in only 7 of 15 cases.In cells cultured from the 10 mixed adenomas that secreted both GH and PRL, RT-PCR analysis revealed a consistent coexpression of SSTR5, SSTR2, and SSTR1 mRNA. In all cases SRIF14, SRIF28, and the SSTR5-preferential analog, BIM-23268, significantly suppressed PRL, secretion, with a mean maximal inhibition of 48 +/- 4%. In contrast, the SSTR2-preferential analogs, BIM-23197 and octreotide, were effective in suppressing PRL in only 6 of 10 cases. In cells cultured from adenomas taken from patients partially responsive to the SRIF analog, octreotide, partial additivity in suppressing both GH and PRL secretion was observed when the SSTR2- and SSTR5-preferring analogs, BIM-23197 and BIM-23268, were tested in combination. Our data show a highly variable ratio of the SSTR2 and SSTR5 transcripts, according to tumors. The SSTR2-preferring compound consistently inhibits GH release, whereas the SSTR5-preferring compound is the main inhibitor of PRL secretion. When both drugs are combined, the partial additivity observed in mixed GH- plus PRL-secreting adenomas may be of interest in the therapeutic approach of such tumors.