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 Citations (Scopus)

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 1 2005

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Cell signaling
Cell death
Gonadotropin-Releasing Hormone
Prostatic Neoplasms
Cell Death
Hormone Antagonists
Cells
LHRH Receptors
Ryanodine Receptor Calcium Release Channel
Inositol
Cell proliferation
Androgens
Labeling
Carrier Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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Differential effects of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on prostate cancer cell signaling and death. / Kaushik, Maiti; Oh, Dayoung; Jung, Sun Moon; Sujata, Acharjee; Jian, Hua Li; Dong, Gyu Bai; Hee-Sae, Park; Keesook, Lee; Young, Chul Lee; Neon, Chul Jung; Kyungjin, Kim; Hubert, Vaudry; Hyuk, Bang Kwon; Jae, Young Seong.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 7, 01.07.2005, p. 4287-4298.

Research output: Contribution to journalArticle

Kaushik, M, Oh, D, Jung, SM, Sujata, A, Jian, HL, Dong, GB, Hee-Sae, P, Keesook, L, Young, CL, Neon, CJ, Kyungjin, K, Hubert, V, Hyuk, BK & Jae, YS 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, vol. 90, no. 7, pp. 4287-4298. https://doi.org/10.1210/jc.2004-1894
Kaushik, Maiti ; Oh, Dayoung ; Jung, Sun Moon ; Sujata, Acharjee ; Jian, Hua Li ; Dong, Gyu Bai ; Hee-Sae, Park ; Keesook, Lee ; Young, Chul Lee ; Neon, Chul Jung ; Kyungjin, Kim ; Hubert, Vaudry ; Hyuk, Bang Kwon ; Jae, Young Seong. / Differential effects of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on prostate cancer cell signaling and death. In: Journal of Clinical Endocrinology and Metabolism. 2005 ; Vol. 90, No. 7. pp. 4287-4298.
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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.",
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AU - Kaushik, Maiti

AU - Oh, Dayoung

AU - Jung, Sun Moon

AU - Sujata, Acharjee

AU - Jian, Hua Li

AU - Dong, Gyu Bai

AU - Hee-Sae, Park

AU - Keesook, Lee

AU - Young, Chul Lee

AU - Neon, Chul Jung

AU - Kyungjin, Kim

AU - Hubert, Vaudry

AU - Hyuk, Bang Kwon

AU - Jae, Young Seong

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N2 - 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.

AB - 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.

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