The growth hormone-releasing hormone (GHRH) antagonist JV-1-36 inhibits proliferation and survival of human ectopic endometriotic stromal cells (ESCs) and the T HESC cell line
The growth hormone-releasing hormone (GHRH) antagonist JV-1-36 inhibits proliferation and survival of human ectopic endometriotic stromal cells (ESCs) and the T HESC cell line
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DOI：
10.1016/j.fertnstert.2009.03.093
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发表时间：
2010-08-01
影响因子：
6.7
通讯作者：
Granata, Riccarda
中科院分区：
文献类型：
--
作者：
Annunziata, Marta;Grande, Cristina;Granata, Riccarda
目的：研究GHRH拮抗剂JV-1-36对原代异位人子宫内膜间质细胞（ESCs）和THESC细胞系增殖和存活的影响。设计：前瞻性实验室研究。地点：大学医院。患者：22名子宫内膜异位症妇女（年龄34.8 +/- 5.7岁）接受治疗性腹腔镜检查。干预：从接受腹腔镜手术治疗子宫内膜异位症的妇女中收集在位（n=10）和异位（n=22）子宫内膜组织主要结果测量：通过逆转录聚合酶链反应（RT-PCR）测定GHRH、GHRH受体（GHRH-R）和GHRH-R剪接变体（SV）1 mRNA的表达。用5-溴-2-脱氧尿苷掺入法检测细胞增殖，用4，5-二甲基噻唑-2-基-2，5-二苯基四氮唑蓝（MTT）比色法和台盼蓝法检测细胞存活率。用MTT法、ELISA法检测细胞内cAMP水平、Western blot法检测细胞外信号调节激酶1和2（ERK 1/2）磷酸化水平、实时荧光定量PCR法检测IGF-2 mRNA的表达。在正常子宫内膜组织、ESC和T HESC中测定了SV 1 mRNA;在T HESC中发现了GHRH mRNA; JV-1-36抑制ESC增殖以及ESC和T HESC存活。结论：GHRH拮抗剂JV-1 - 36抑制子宫内膜异位症细胞增殖和存活，提示GHRH拮抗剂可能是治疗子宫内膜异位症的有效药物。（Fertil Steril（R）2010; 94：841-9. (c)美国生殖医学会（American Society for Reproductive Medicine）
Objective: To determine the effect of the GHRH antagonist JV-1-36 on proliferation and survival of primary ectopic human endometriotic stromal cells (ESCs) and the T HESC cell line.Design: Prospective laboratory study.Setting: University hospital.Patient(s): 22 women with endometriosis (aged 34.8 +/- 5.7 years) undergoing therapeutic laparoscopy.Intervention(s): Eutopic (n=10) and ectopic (n=22) endometrial tissues were collected from women who underwent therapeutic laparoscopic surgery for endometriosis (stage III/IV).Main Outcome Measure(s): Expression of GHRH, GHRH receptor (GHRH-R) and GHRH-R splice variant (SV) 1 mRNA was determined by reverse-transcription polymerase chain reaction (RT-PCR). The ESC proliferation was assessed by 5-bromo-2-deoxyuridine incorporation, cell survival by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and Trypan blue assay. The T HESC survival was evaluated by MTT, cyclic adenosine monophosphate (cAMP) levels by ELISA, extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation by Western blot, and insulin-like growth factor (IGF)-2 mRNA by real-time PCR.Result(s): The ESCs and T HESCs, but not normal endometrial tissues, expressed GHRH-R mRNA; SV1 mRNA was determined in normal endometrial tissues, ESCs, and T HESCs; GHRH mRNA was found in T HESCs; JV-1-36 inhibited ESC proliferation and ESC and T HESC survival. In T HESCs, JV-1-36 reduced cAMP production and ERK1/2 phosphorylation but had no effect on IGF-2 mRNA expression.Conclusion(s): The GHRH antagonist JV-1-36 inhibits endometriotic cell proliferation and survival, suggesting that GHRH antagonist may represent promising tools for treatment of endometriosis. (Fertil Steril (R) 2010; 94: 841-9. (c) 2010 by American Society for Reproductive Medicine.)