Differential effects of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on prostate cancer cell signaling and death

Maiti Kaushik, Dayoung Oh, Sun Moon Jung, Acharjee Sujata, Hua Li Jian, Gyu Bai Dong, Park Hee-Sae, Lee Keesook, Chul Lee Young, Chul Jung Neon, Kim Kyungjin, Vaudry Hubert, Bang Kwon Hyuk, Young Seong Jae

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Context: GnRH is known to directly regulate prostate cancer cell proliferation, but the precise mechanism of action of the peptide is still under investigation. Objective: This study demonstrates differential effects of GnRH-I and GnRH-II on androgen-independent human prostate cancer cells. Results: Both GnRH-I and GnRH-II increased the intracellular Ca2+ concentration ([Ca2+]i) either through Ca2+ influx from external Ca2+ source or via mobilization of Ca 2+ from internal Ca2+ stores. Interestingly, the [Ca 2+]i increase was mediated by activation of the ryanodine receptor but not the inositol trisphosphate receptor. Trptorelix-1, a novel GnRH-II antagonist but not cetrorelix, a classical GnRH-I antagonist, completely inhibited the GnRH-II-induced [Ca2+]i increase. Concurrently at high concentrations, trptorelix-1 and cetrorelix inhibited GnRH-I-induced [Ca2+]i increase, whereas at low concentrations they exerted an agonistic action, inducing Ca2+ influx. High concentrations of trptorelix-1 but not cetrorelix-induced prostate cancer cell death, probably through an apoptotic process. Using photoaffinity labeling with 125I-[azidobenzoyl-D-Lys6]GnRH-II, we observed that an 80-kDa protein specifically bound to GnRH-II. Conclusions: This study suggests the existence of a novel GnRH-II binding protein, in addition to a conventional GnRH-I receptor, in prostate cancer cells. These data may facilitate the development of innovatory therapeutic drugs for the treatment of prostate cancer.

Original languageEnglish (US)
Pages (from-to)4287-4298
Number of pages12
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number7
DOIs
StatePublished - Jul 2005

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Kaushik, M., Oh, D., Jung, S. M., Sujata, A., Jian, H. L., Dong, G. B., Hee-Sae, P., Keesook, L., Young, C. L., Neon, C. J., Kyungjin, K., Hubert, V., Hyuk, B. K., & Jae, Y. S. (2005). Differential effects of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on prostate cancer cell signaling and death. Journal of Clinical Endocrinology and Metabolism, 90(7), 4287-4298. https://doi.org/10.1210/jc.2004-1894