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: RESULTS: Both GnRH-I and GnRH-II increased the intracellular Ca(2+) concentration ([Ca(2+)](i)) either through Ca(2+) influx from external Ca(2+) source or via mobilization of Ca(2+) from internal Ca(2+) 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 [Ca(2+)](i) increase. Concurrently at high concentrations, trptorelix-1 and cetrorelix inhibited GnRH-I-induced [Ca(2+)](i) increase, whereas at low concentrations they exerted an agonistic action, inducing Ca(2+) influx. High concentrations of trptorelix-1 but not cetrorelix-induced prostate cancer cell death, probably through an apoptotic process. Using photoaffinity labeling with (125)I-[azidobenzoyl-D-Lys(6)] GnRH-II, we observed that an 80-kDa protein specifically bound to GnRH-II. CONCLUSIONS:
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Authors | Kaushik Maiti, D Y Oh, Da Young Oh, 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 |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 90
Issue 7
Pg. 4287-98
(Jul 2005)
ISSN: 0021-972X [Print] United States |
PMID | 15870130
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- GNRHR2 protein, human
- Inositol Phosphates
- Photoaffinity Labels
- Receptors, LHRH
- Ryanodine Receptor Calcium Release Channel
- Gonadotropin-Releasing Hormone
- LHRH, His(5)-Trp(7)-Tyr(8)-
- Calcium
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Topics |
- Apoptosis
- Calcium
(metabolism)
- Gonadotropin-Releasing Hormone
(analogs & derivatives, antagonists & inhibitors, pharmacology)
- Humans
- Inositol Phosphates
(metabolism)
- Male
- Photoaffinity Labels
- Prostatic Neoplasms
(metabolism, pathology)
- Receptors, LHRH
(analysis, physiology)
- Reverse Transcriptase Polymerase Chain Reaction
- Ryanodine Receptor Calcium Release Channel
(drug effects)
- Signal Transduction
(physiology)
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