Korean J Urol.  1997 Sep;38(9):963-972.

Detection of the Expression of GnRH and GnRH Receptor mRNAs and Effect of GnRH on Prostate Cancer Cell Proliferation

Affiliations
  • 1Department of Urology, Gyeongsang National University, Mediccal College, Chinju, Korea.

Abstract

Prostatic cancer is the typical hormone dependant cancer and several kinds of hormones are used for the treatment of prostate cancer. Since Harris had proposed the hypothalamo-pituitary gonadal axis, the hypothalamus is believed the exclusive organ producing GnRH. According to the recent researches, several organs were proved to be the extrahypothalamic GnRH sources in human and animal. In this research, the expression of the GnRH and GnRH receptor mRNA, detection of the GnRH which prostate cancer cell produced and effect of the GnRH on the prostate cancer cell proliferation using three human prostate cancer cell lines, ALVA 41, ALVA 101 and DU-145 were studied. In Situ Hybridization method was used for the detection of the expression of the GnRH and GnRH receptor mRNA. The charcoal stripped serum and high performance liquid chromatography were used for the detection of the GnRH produced from prostate cancer cells. Thymidine incorporation assay was used for the evaluation of the effect of the GnRH on the prostate cancer cell proliferation. The GnRH mRNA were detected in 96.7% of ALVA 41, 91.5% of ALVA 101 and 95.3% of DU-145 and GnRH receptor mRNA expression signals were detected in almost all of the examined prostate cancer cells, more than 95%, in three cell lines. The number of signals of the GnRH receptor mRNA were more than GnRH mRNA. The GnRH produced from the rostate cancer cell was detected at culture medium with retention time 19.40 minutes. The cancer cells cultured with peptide hormone deficient medium using charcoal stripped serum showed more than 20% growth retardation to the cancer cells grown at the medium used normal serum. The treatment of the GnRH on the cancer cells growing at the peptide hormone deficient medium showed statistically insignificant dose dependant growth retardation. The RESULTS of our research showed that the human prostate cancer cells, including two hormone refractory prostate cancer cell lines, produce the GnRH and the GnRH receptor in the same cell which could be suggest that the role of GnRH produced from the prostate cancer cell would be autocrine action. And the prostate cancer cell growth was down regulated by unknown complex of various peptide hormones and the GnRH does not has the significant effect on the proliferations of the prostate cancer cells. With those RESULTS we obtained in this research and other's data, it seems that there is a system that contains production of GnRH and GnRH receptor and metabolic mechinary within prostate cancer cell. And there should be the some changes in the hypothalamo-pituitary gonadal axis and the mechanism using GnRH analogues for the treatment of prostate cancer aside from central mechanism.

Keyword

GnRII; GnRII; receptor mRNA; ALVA 41; ALVA 101; DU-145; Prostate cancer
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