Gonadotropin-releasing hormone (GnRH) produced within ovarian cancers and endometrial cancers acts as a negative autocrine regulator in their growth. To provide a potential association of GnRH content with the presence of GnRH receptor, we have evaluated GnRH levels in human gynecologic carcinomas and compared them to those in normal tissues. Surgically removed tumors and normal tissues had been screened for GnRH receptor expression before analysis. GnRH was determined by a radioimmunoassay and a high-perfomance liquid chromatography in peptide extracts. GnRH levels for ovarian cancers (n=25, range 0.01- 0.99 pg/mg protein, with a mean ± SD of 0.37±0.28 pg/mg protein) and for endometrial cancers (n=12, range 0.01-0.19, 0.13±0.074 pg/mg protein) were significantly higher than those for normal ovaries (n=11, range 0.007-0.195, 0.10±0.06 pg/mg protein) (P=0.003) and endometria (n=7, range 0.01-0.09, 0.049±0.029 pg/mg protein) (P=0.014), respectively. The GnRH levels in these cancers were not different between GnRH receptor-positive specimens (20 ovarian cancers and 9 endometrial cancers) and -negative specimens (5 ovarian cancers and 3 endometrial cancers). In contrast, GnRH was <0.001 pg/mg protein in all 13 uterine cervical carcinomas bearing no GnRH receptor. These data demonstrate that the neoplastic ovaries and endometria that frequently express GnRH receptor have the capacity to produce excessive amount of GnRH regardless of whether GnRH receptor is evident.

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