Expression of Gonadotropin-Releasing Hormone Receptor in Human Uterine Endometrial and Ovarian Tissues / 대한암학회지

ABSTRACT

PURPOSE: Gonadotropin-releasing hormone (Gn-RH) can cause regression of hormonedependent human tumors, including uterine endometrial and ovarian carcinomas. These effects were thought to be mediated through the inhibition of gonadotropic and steroid hormone from the hypothalamus. But, in addition to its classic hypophysiotropic action, Gn-RH might play a role as a modulator of activity in the brain and many peripheral organs. It has been reported that this analog has a direct inhibitory effect on the tumor and that the specific binding sites for Gn-RH were demonstrated in certain tumors responsive to Gn-RH. In support of a possible clinical use of Gn-RH analogs in the treatment of the endometrial and ovarian carcinomas, we tried to find out whether Gn-RH receptors are present on hormone dependent tumors. MATERIALS AND METHODS: We have studied endometrial and ovarian tumor specimens and established uterine endometrial and ovarian carcinoma cell lines for the presence of Gn-RH receptor by the detection of its messenger ribonucleic acid (mRNA). We also compared the results obtained from tumor tissue specimens with the results from their corresponding normal tissues. Gn-RH receptor mRNA was determined by reverse transcription-polymerase chain reaction using oligonucleotide primers synthesized according to the published human Gn-RH receptor sequence. RESULTS: Gn-RH receptor mRNA was detected in all normal endometrium and abnormally proliferative endometrium presenting dysfunctional bleeding, but not all in endometrial carcinomas (83%). Tumor stage and histologic grading had no relationship with receptor positivity. And, Gn-RH receptor mRNA was detected in less than 40% in normal myometrium and myomas. Gn-RH receptor expression was detected in same frequencies (86%) in normal ovarian tissues and ovarian carcinomas. Receptors were detected in a high proportion of the specimens from epithelial carcinomas (92%) and stromal tumors (100%) of the ovary. But, Gn-RH receptor was not detected in germ-cell derived tumors of the ovary. Established endometrial carcinoma (CUME-1) and epithelial ovarian carcinoma (CUMO-2) cell lines also demonstrated Gn-RH receptor mRNA, respectively. CONCLUSIONS: The expression of Gn-RH receptor raises the possibility that Gn-RH may play a direct regulatory role in the growth of hormone-dependent normal tissues and their respective tumors, and provides a possible point of attack for therapeutic approaches using Gn-RH analogs in endometrial and ovarian malignancies.