Irmer G, Bürger C, Müller R, Ortmann O, Peter U, Kakar S S, Neill J D, Schulz K D, Emons G
Department of Obstetrics and Gynecology, Philipps University, Marburg, Germany.
Cancer Res. 1995 Feb 15;55(4):817-22.
Recently we reported the presence of specific high affinity binding sites for luteinizing hormone-releasing hormone (LHRH) and its analogues (Kd = 1.5 or 1.7 nM) in the human epithelial ovarian cancer cell lines EFO-21 and EFO-27. The proliferation of these cell lines was inhibited by nM concentrations of a LHRH agonist. This study was performed to ascertain whether these ovarian cancer cell lines produce LHRH and whether the high affinity LHRH binding site found previously was identical to the pituitary LHRH receptor. Significant amounts of immunoreactive LHRH were found in the extracts of both the EFO-21 cell line (449 +/- 56 fmol/10(6) cells) and the EFO-27 line (409 +/- 76 fmol/10(6) cells). LHRH bioactivity of these extracts, assessed in terms of release of luteinizing hormone by rat pituitary cells, was comparable to that of authentic LHRH. EFO-21 and EFO-27 cells expressed the mRNAs for both human LHRH and human LHRH receptor as assessed by reverse transcriptase-PCR using oligonucleotide primers according to published sequences. In addition, in eight of eight biopsy samples of human epithelial ovarian cancers we detected mRNA for LHRH, six of these specimens expressed the mRNA representing the LHRH receptor. These data support the concept that human epithelial ovarian cancers might have a local system based on LHRH to regulate cell proliferation. It is still obscure at present whether LHRH produced locally has a stimulatory, inhibitory, or no impact on the proliferation of ovarian cancer cells. However, exogenous LHRH agonists seem to have clear antiproliferative activity, probably mediated through LHRH receptors. This finding might provide the base for novel approaches in the therapy of epithelial ovarian cancer.
最近我们报道了在人上皮性卵巢癌细胞系EFO - 21和EFO - 27中存在促黄体生成激素释放激素（LHRH）及其类似物的特异性高亲和力结合位点（解离常数Kd = 1.5或1.7 nM）。这些细胞系的增殖受到纳摩尔浓度的LHRH激动剂的抑制。本研究旨在确定这些卵巢癌细胞系是否产生LHRH，以及先前发现的高亲和力LHRH结合位点是否与垂体LHRH受体相同。在EFO - 21细胞系提取物（449±56 fmol/10⁶细胞）和EFO - 27细胞系提取物（409±76 fmol/10⁶细胞）中均发现了大量免疫反应性LHRH。根据大鼠垂体细胞促黄体生成激素的释放评估，这些提取物的LHRH生物活性与天然LHRH相当。通过使用根据已发表序列设计的寡核苷酸引物进行逆转录 - PCR评估，EFO - 21和EFO - 27细胞表达人LHRH和人LHRH受体的mRNA。此外，在8例人上皮性卵巢癌活检样本中，我们均检测到LHRH的mRNA，其中6例标本表达代表LHRH受体的mRNA。这些数据支持这样一种概念，即人上皮性卵巢癌可能具有基于LHRH的局部系统来调节细胞增殖。目前尚不清楚局部产生的LHRH对卵巢癌细胞增殖是具有刺激、抑制还是无影响。然而，外源性LHRH激动剂似乎具有明显的抗增殖活性，可能是通过LHRH受体介导的。这一发现可能为上皮性卵巢癌的新治疗方法提供基础。
