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Direct anticancer activity of gonadotropin-releasing hormone-III.

Abstract
In previous studies GnRH-III, a variant of the hypothalamic neurohormone GnRH, was isolated from the brain of the sea lamprey and structurally characterized. GnRH-III is a hypothalamic neurohormone in both female and male sea lampreys. In the present work biological activities of GnRH-III in mammalian systems were examined. In superfused rat pituitary cells, GnRH-III at 1 nM to 100 nM neither induced LH-secretion nor inhibited the LH-secretion elicited by native GnRH and elicited LH release only at 1 microM. At high dose (500 microg/day) in vivo, GnRH-III behaved as a GnRH agonist, though, it was 1000-fold less active than ovurelin. The in vitro and in vivo results were in good agreement in showing that GnRH-III is only a weak agonist of the endocrine activity of GnRH. GnRH-III specifically bound to receptors on cancer cells and recognized not only the high-, but also the low-affinity binding sites. GnRH-III significantly suppressed growth of human cancer cells which have GnRH receptors. The inhibitory effect of GnRH-III on growth of cancer cells was specific and direct since the peptide did not have endocrine activity in the concentration range found to be effective in anticancer assays. GnRH-III inhibited equally the growth of ER-positive and -negative breast and TeR-positive and negative prostate cells.
AuthorsS Lovas, I Pályi, B Vincze, J Horváth, M Kovács, I Mezö, G Tóth, I Teplán, R F Murphy
JournalThe journal of peptide research : official journal of the American Peptide Society (J Pept Res) Vol. 52 Issue 5 Pg. 384-9 (Nov 1998) ISSN: 1397-002X [Print] Denmark
PMID9894843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Antineoplastic Agents
  • Receptors, LHRH
  • Gonadotropin-Releasing Hormone
  • Luteinizing Hormone
Topics
  • Animals
  • Antineoplastic Agents (metabolism, pharmacology)
  • Cell Division (drug effects)
  • Female
  • Gonadotropin-Releasing Hormone (metabolism, pharmacology)
  • Humans
  • Luteinizing Hormone (metabolism)
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, LHRH (metabolism)
  • Tumor Cells, Cultured

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