Alternative gonadotropin-releasing hormone processing products secreted from endometrial carcinoma

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