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Somatostatin receptor subtype 1 selective activation in human growth hormone- and prolactin-secreting pituitary adenomas: effects on cell viability, growth hormone and prolactin secretion.

机译:生长激素受体亚型1在人生长激素和催乳素分泌的垂体腺瘤中的选择性激活:对细胞活力,生长激素和催乳素分泌的影响。

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摘要

Somatostatin (SRIF) analogs interacting with SRIF receptor subtype (SSTR) 2 and SSTR5 are known to reduce secretion in GH-secreting pituitary adenomas. We investigated the effects of SRIF and a SSTR1 selective agonist, BIM-23926, on GH and prolactin (PRL) secretion and cell viability in primary cultures deriving from 15 GH- and PRL-secreting adenomas expressing SSTR1. Quantitative RT-PCR showed SSTR1 mRNA mean levels of 6 +/- 2.2 x 10(4) molecules/ microg reverse-transcribed total RNA. SSTR2 and SSTR5 were frequently expressed (93.3%), on the contrary of SSTR3 (53.3%) and SSTR4 (6.7%). GH secretion was significantly reduced by SRIF and BIM-23926 (45 +/- 8.6% and 32 +/- 18.1% inhibition, respectively) as well as PRL secretion (16.1 +/- 4% and 19.7 +/- 3.5% inhibition, respectively). After treatment with SRIF and BIM-23926, cell viability was significantly reduced by 17.5 +/- 5% and 20 +/- 3.9%, respectively. SSTR1 mRNA levels correlated with the degree of GH and PRL secretion inhibition. These results demonstrate that SSTR1 selective activation inhibits hormone secretion and cell viability in GH- and PRL-secreting adenomas in vitro and suggest that SRIF analogs with affinity for SSTR1 may be useful to control hormone hypersecretion and reduce neoplastic growth of pituitary adenomas.
机译:已知与SRIF受体亚型(SSTR)2和SSTR5相互作用的生长抑素(SRIF)类似物可减少GH分泌垂体腺瘤的分泌。我们调查了SRIF和SSTR1选择性激动剂BIM-23926对GH和催乳素(PRL)分泌和细胞存活率的影响,这些分泌和细胞活力来自表达SSTR1的15个分泌GH和PRL的腺瘤。定量RT-PCR显示SSTR1 mRNA平均水平为6 +/- 2.2 x 10(4)分子/微克逆转录总RNA。 SSTR2和SSTR5经常表达(93.3%),而SSTR3(53.3%)和SSTR4(6.7%)相反。 SRIF和BIM-23926(分别抑制45 +/- 8.6%和32 +/- 18.1%)以及PRL分泌(16.1 +/- 4%和19.7 +/- 3.5%,分别)。用SRIF和BIM-23926处理后,细胞活力分别显着降低了17.5 +/- 5%和20 +/- 3.9%。 SSTR1 mRNA水平与GH和PRL分泌抑制的程度相关。这些结果表明,SSTR1选择性激活在体外抑制GH和PRL分泌腺瘤中的激素分泌和细胞活力,并表明对SSTR1具有亲和力的SRIF类似物可用于控制激素过度分泌并减少垂体腺瘤的赘生性生长。

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