Direct anticancer activity of gonadotropin-releasing hormone-III

Sándor Lovas, I. Pályi, B. Vincze, J. Horváth, M. Kovács, I. Mezö, G. Tóth, I. Teplán, R. F. Murphy

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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 μM. At high dose (500 μg/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.

Original languageEnglish (US)
Pages (from-to)384-389
Number of pages6
JournalJournal of Peptide Research
Volume52
Issue number5
DOIs
StatePublished - Jan 1 1998

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology

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    Lovas, S., Pályi, I., Vincze, B., Horváth, J., Kovács, M., Mezö, I., Tóth, G., Teplán, I., & Murphy, R. F. (1998). Direct anticancer activity of gonadotropin-releasing hormone-III. Journal of Peptide Research, 52(5), 384-389. https://doi.org/10.1111/j.1399-3011.1998.tb00662.x