Alternative gonadotropin-releasing hormone I and II processing products secreted from endometrial carcinoma

促性腺激素释放激素(GnRH)受体在子宫内膜癌中有表达。子宫内膜癌也会产生GnRH或类似的多肽，这促使我们检查肿瘤内的GnRH是否作为其受体的天然配体。在分析之前，对手术切除的子宫内膜癌进行了促性腺激素释放激素受体的筛查。对子宫内膜癌细胞培养上清液中的GnRH进行免疫印迹分析和氨基酸序列测定。在10例子宫内膜癌标本中均检测到Pre-proGnRH、ProGnRH和十肽GnRH三种主要蛋白，分别为10.0 kDa、7.6 kDa和1.1 kDa。放射免疫法测定培养上清液中GnRH的免疫活性含量为0.08~0.1nM。在绒毛细胞条件培养液中，仅检测到1.1 kDa的蛋白。子宫内膜癌细胞除了分泌天然的促性腺激素释放激素外，还会分泌其他促性腺激素释放激素的加工产物。GnRH突变体可能在其受体水平上与成熟的GnRH竞争，可能通过阻断GnRH信号通路来延缓细胞增殖。

Gonadotropin-releasing hormone (GnRH) receptor is demonstrated in uterine endometrial carcinoma. The endometrial carcinoma also produces GnRH or -like peptide, which prompted us to examine whether the intratumoral 'GnRH' serves as natural ligand for its receptor. Endometrial carcinomas surgically removed had been screened for GnRH receptor expression before analysis. The 'GnRH' in endometrial carcinoma cell-enriched culture media was characterized by immunoblots in tricine-supplied electrophoresis system and subsequent amino acid sequencing. Three major proteins of 10.0kDa,7.6kDa and 1.1kDa corresponding to pre-proGnRH, proGnRH and decapeptide GnRH, respectively, were detected in all of ten endometrial carcinoma specimens tested. Immunoreactive 'GnRH' contents in the culture media, assessed by RIA, ranged from 0.08 to 0.1nM. In chorionic cells-conditioned media, only 1.1-kDa protein was detected. Endometrial carcinoma cells secrete alternative GnRH processing products in addition to natural GnRH. The GnRH variants may compete with mature GnRH at the level of its receptors, perhaps counteracting GnRH signaling pathway to retard cell proliferation.