Interdisziplinäres Stoffwechsel-Centrum, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
Eur J Endocrinol. 2012 Feb;166(2):223-34. doi: 10.1530/EJE-11-0737. Epub 2011 Nov 7.
Somatostatin analogues (SSA) reduce autonomous GH secretion by activating somatostatin receptors (sst) 2 and 5 in 50-60% of acromegalic patients. However, by inhibiting insulin secretion these SSA reduce glucose tolerance. DG3173 is a novel SSA with additional binding to sst4 and low insulin-suppressing activity. We investigated the effect of DG3173, including its relation to specific tumour characteristics, on GH secretion in human somatotroph adenoma cell cultures (hSA) in comparison with Octreotide.
Twenty-seven hSA were characterised immunohistochemically for their hormone- and sst-expression, granularity and pre-surgical therapy with SSA. GH was determined in supernatants of hSA treated with DG3173 or Octreotide in time- (n=6) and dose-response (n=21) experiments. A positive response was defined as GH suppression to below 80% of baseline.
In the dose-response experiments DG3173 suppressed GH secretion in more adenomas than Octreotide (10/21 vs 5/21), including 38% (6/16) of Octreotide non-responders. In responders the extent of GH suppression and IC(50) were comparable for both SSA. The response-rate of both SSA was higher in monohormonal vs bihormonal adenomas, yet GH declined similarly in both groups. Neither pre-surgical SSA (n=6) nor tumour morphology was related to the GH response. However, semi-quantitative analysis indicated a small but significant negative correlation between the GH response to Octreotide and the immunoreactivity scores of sst2 expression.
DG3173 equalled Octreotide in suppressing GH secretion in hSA. Since DG3173 suppressed GH in some Octreotide-non-responsive adenomas, its clinical effectiveness will be worth testing. Moreover, its reduced insulin-suppressive potency would make it a valuable alternative to Octreotide.
生长抑素类似物（SSA）通过激活生长抑素受体（sst）2 和 5 来减少 50-60%肢端肥大症患者的自主 GH 分泌。然而，这些 SSA 通过抑制胰岛素分泌来降低葡萄糖耐量。DG3173 是一种新型 SSA，与 sst4 具有额外的结合，并且胰岛素抑制活性较低。我们研究了 DG3173 的作用，包括其与特定肿瘤特征的关系，对人垂体腺瘤细胞培养物（hSA）中 GH 分泌的影响，与奥曲肽进行比较。
通过免疫组织化学方法对 27 例 hSA 的激素和 sst 表达、颗粒度以及术前 SSA 治疗进行了特征描述。通过时间（n=6）和剂量反应（n=21）实验，在 DG3173 或奥曲肽处理的 hSA 上清液中测定 GH。将 GH 抑制率低于基础值的 80%定义为阳性反应。
在剂量反应实验中，DG3173 抑制 GH 分泌的腺瘤比奥曲肽多（10/21 比 5/21），包括 38%（6/16）的奥曲肽无反应者。在有反应者中，两种 SSA 对 GH 的抑制程度和 IC50 相当。两种 SSA 的反应率在单激素腺瘤与双激素腺瘤中均较高，但两组的 GH 下降相似。术前 SSA（n=6）或肿瘤形态均与 GH 反应无关。然而，半定量分析表明，奥曲肽的 GH 反应与 sst2 表达的免疫反应评分之间存在小但显著的负相关。
DG3173 在抑制 hSA 中的 GH 分泌方面与奥曲肽相当。由于 DG3173 抑制了一些奥曲肽无反应的腺瘤中的 GH，因此其临床疗效值得一试。此外，其降低的胰岛素抑制作用使其成为奥曲肽的一种有价值的替代物。
